Tami Denise John

All Publications

• Clinical Hematopoietic Stem Cell-Based Gene Therapy. Molecular therapy : the journal of the American Society of Gene Therapy John, T., Czechowicz, A. 2025

  Abstract

  Hematopoietic stem cell (HSC)-based gene therapies have seen extraordinary progress since their initial conception, now fundamentally transforming the treatment paradigms for various inherited hematologic, immunologic and metabolic conditions - with additional use cases under exploration. Decades worth of work with advances in viral vector technologies and cell manufacturing have paved the way for HSC gene therapy with marked improvement in the safety and efficiency of gene delivery into HSCs. These have been augmented by the recent rise of innovative genome editing techniques, particularly using clustered regularly interspaced short palindromic repeats - CRISPR-associated proteins (CRISPR-Cas)-based technologies, which have enabled more precise and reproducible genome alterations in HSCs and fostered opportunities for targeted gene modification or gene correction. These breakthroughs have led to the development of many active clinical trials and culminated in the recent federal regulatory agency approvals of multiple clinical HSC gene therapies for various indications that are now becoming available across different geographies. These treatments aim to offer significant, long-lasting benefits to patients world-wide without the toxicities of alternative treatment approaches. This review explores the history and advancements in HSC gene therapies and provides a comprehensive overview of the latest clinical innovations and cell therapy products. Further, it concludes with a discussion of the persistent challenges that have limited adoption and potential future opportunities that aspire to enable curative treatment of many different patients through such personalized medicines.

  View details for DOI 10.1016/j.ymthe.2025.04.029

  View details for PubMedID 40285354

• Incremental Eligibility Criteria for the BMT CTN 1507 Haploidentical Trial for Children with Sickle Cell Disease. Blood advances John, T. D., Walters, M. C., Rangarajan, H. G., Rahim, M. Q., McKinney, C. M., Bollard, C. M., Abusin, G., Eapen, M., Kassim, A. A., DeBaun, M. R. 2024

  Abstract

  The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the Data Safety Monitoring Board (DSMB) established incremental entry criteria for children aged 5-14.99 years with sickle cell disease (SCD) enrolling on a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation (clinicaltrials.gov #NCT032635590). First, enrollment was limited to overt stroke in the first 10 participants (Stage 4). Subsequently, the DSMB reviewed the interim results and expanded eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography-defined cerebral vasculopathy (Stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n=18). Additions to the entry criteria included non-neurologic morbidities (Stage 2). Eligibility criteria included: a) life-threatening acute chest syndrome requiring exchange transfusion, b) right heart catheterization confirmed pulmonary hypertension, c) persistent systemic hypertension despite maximum medical therapy, d) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication, or e) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. For the first time, we introduce a staged strategy to eligibility for a curative therapy trial for children with SCD concordant with 45 CFR § 46.405(b). The research governance-mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials.

  View details for DOI 10.1182/bloodadvances.2024014078

  View details for PubMedID 39374573

• Dismantling cost and infrastructure barriers to equitable access to gene therapies for sickle cell disease. The Lancet. Haematology Sharma, A., John, T. D. 2024

  View details for DOI 10.1016/S2352-3026(24)00175-3

  View details for PubMedID 38964356

• Strategic infection prevention after genetically modified hematopoietic stem cell therapies: recommendations from the International Society for Cell & Gene Therapy Stem Cell Engineering Committee. Cytotherapy John, T. D., Maron, G., Abraham, A., Bertaina, A., Bhoopalan, S. V., Bidgoli, A., Bonfim, C., Coleman, Z., DeZern, A., Li, J., Louis, C., Oved, J., Pavel-Dinu, M., Purtill, D., Ruggeri, A., Russell, A., Wynn, R., Boelens, J. J., Prockop, S., Sharma, A. 2024

  Abstract

  There is lack of guidance for immune monitoring and infection prevention after administration of ex vivo genetically modified hematopoietic stem cell therapies (GMHSCT). We reviewed current infection prevention practices as reported by providers experienced with GMHSCTs across North America and Europe, and assessed potential immunologic compromise associated with the therapeutic process of GMHSCTs described to date. Based on these assessments, and with consensus from members of the International Society for Cell & Gene Therapy (ISCT) Stem Cell Engineering Committee, we propose risk-adapted recommendations for immune monitoring, infection surveillance and prophylaxis, and revaccination after receipt of GMHSCTs. Disease-specific and GMHSCT-specific considerations should guide decision making for each therapy.

  View details for DOI 10.1016/j.jcyt.2024.02.005

  View details for PubMedID 38483362

• Red Cell Rheology and Blood Viscosity in Pediatric Individuals Having Received Allogenic Hematopoietic Stem Cell Transplantation or Ex Vivo Autologous Gene Therapy for Sickle Cell Disease Patel, A. P., Kanne, C. K., Stenger, E. O., John, T. D., Sheehan, V. A. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-188045

  View details for Web of Science ID 001159306704100

• Regimen Intensity and Age Affect Transplant-Related Outcomes after Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Registry Study John, T. D., Chellapandian, D., Shah, R., Gillespie, S., Liu, K., Xiang, Y., Bhatia, M., Chaudhury, S., Eckrich, M. J., Guilcher, G. T., Jaroscak, J., Kasow, K. A., Krajewski, J., Ngwube, A. I., Olson, T. S., Rangarajan, H. G., Horan, J. T., Krishnamurti, L., Shenoy, S., Abraham, A., Stenger, E. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182532

  View details for Web of Science ID 001159900800105

• Donor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study Stenger, E., John, T. D., Chellapandian, D., Shah, R., Gillespie, S., Xiang, Y., Liu, K., Bhatia, M., Guilcher, G. T., Jaroscak, J., Kasow, K. A., Krajewski, J., Ngwube, A. I., Rangarajan, H. G., Horan, J. T., Krishnamurti, L., Shenoy, S., Abraham, A. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023188514

  View details for Web of Science ID 001159900800156