Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation

Summary

Background: Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems. Eligibility: Donors: Healthy people ages 4 and older Recipients: People the same age with abnormal T-cell function causing health problems Design: All participants will be screened with: * Medical history * Physical exam * Blood, heart, and urine tests Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test. Recipients will also have lung tests. Some participants will have scans and/or bone marrow collected by needle in the hip bones. Donors will learn about medicines and activities to avoid and repeat some screening tests. Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia. Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm. Recipients will have: * More bone marrow and a small fragment of bone removed * Dental, diet, and social worker consultations * Scans * Chemotherapy and antibody therapy for 2 weeks * Catheter inserted in a chest or neck vein to receive donor stem cells * A hospital stay for several weeks with more medicines and procedures * Multiple follow-up visits

Timeline

Start

2018-09-04

Primary completion

2025-04-03

Completion

2030-04-03

Publications

• Background Dimitrova D, et al. BK virus-associated hemorrhagic cystitis in posttransplant cyclophosphamide-based allogeneic hematopoietic cell transplantation (HCT) for immune deficiency or dysregulation. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation; Glasgow, United Kingdom; April 16, 2024.
• Background Cusmano A, Soldatos A, Notarangelo L, Grimes A, Makkeyah S, Selim L, Kanakry J, Dimitrova D. Allogeneic hematopoietic cell transplantation (HCT) in two pediatric patients with central nervous system-restricted familial hemophagocytic lymphohistiocytosis. The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation; Glasgow, United Kingdom; April 15, 2024. (presenting and senior author)
• Background Cusmano A, Maher J, Gomez-Lobo V, Freeman A, Uzel G, Kanakry JA, Dimitrova D. Ovarian function following reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT): how fertile is the future? Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; San Antonio, TX; February 22, 2024. (presenting and senior author)
• Background Dimitrova D, et al. Pre-Transplant Anti-CD20 Monoclonal Antibody Therapy Affects the Donor-Derived Hematopoietic Compartment in Allogeneic Hematopoietic Cell Transplantation (HCT) Recipients. The 49th Annual Meeting of the European Society for Blood and Marrow Transplantation; Paris, France; April 23-26, 2023.
• Background Dimitrova D, et al. Humoral Reconstitution after Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Pretreated with Targeted Anti-CD20 Therapy. Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; Orlando, FL; February 16, 2023.
• Background Dimitrova D, Napier S, Stokes A, Uzel G, Miljkovic M, Pittaluga S, Wang H, Notarangelo LD, Ombrello AK, Stone D, Cuellar-Rodriguez J, Wilder J, Hicks SN, Sadler JL, Fowler DH, Gress RE, Kanakry CG, Kanakry JA. Distal Equine Anti-Thymocyte Globulin (ATG) As an Adjunct to Reduced Intensity Conditioning and Posttransplantation Cyclophosphamide (PTCy) for Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Benign and Malignant Disorders of T Cell Proliferation or Dysregulation. Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; virtual; February 8-12, 2021.
• Background Dimitrova D, Uzel G, Notarangelo LD, Ombrello AK, Stone D, Parta M, Carroll E, Wilder J, Hicks SN, Sadler JL, Fowler DH, Gress RE, Kanakry CG, Kanakry JA. Novel Reduced Intensity Conditioning (RIC) Approach to Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Benign and Malignant Disorders of T Cell Proliferation or Dysregulation. The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation; virtual; August 2020.
• Background Rechache, Kamil & Dimitrova, Dimana & Feng, Xingmin & Flomerfelt, Francis & Napier, Scott & Sponaugle, Jennifer & Stokes, Anita & Hyder, Mustafa & McKeown, Christi & Wilder, Jennifer & Baruffaldi, Judy & Chai, Amy & Walker, Melissa & Gress, Ronald & Kanakry, Christopher & Kanakry, Jennifer. (2022). Distally-Timed Equine Antithymocyte Globulin (eATG) in Allogeneic Hematopoietic Cell Transplantation (HCT) Conditioning - Pharmacokinetics and the Relationship between Total E-ATG Levels, Pre-HCT Absolute Lymphocyte Count, Immune Reconstitution, and Graft-Versus-Host Responses. Transplantation and Cellular Therapy. 28. S80. 10.1016/S2666-6367(22)00254-8.
• Background Kamil A. Rechache, Natalia S. Nunes, Xingmin Feng, Francis A Flomerfelt, William Telford, Brian Dawson, Thomas E. Hughes, Syed Muhammad Salman Shah, Jennifer Sponaugle, Amy Chai, Jessenia Campos, Mustafa A. Hyder, Dimana Dimitrova, Christopher G. Kanakry, Jennifer A. Kanakry,The Pharmacokinetics and Pharmacodynamics of Distally-Timed Eatg in Allogeneic Hematopoietic Cell Transplantation Conditioning,Transplantation and Cellular Therapy,Volume 31, Issue 2, Supplement,2025,Pages S174-S175,ISSN 2666-6367,https://doi.org/10.1016/j.jtct.2025.01.269.
• Xue E, Das S, Choo-Wosoba H, Dimitrova D, Hyder MA, Flomerfelt FA, Dawson B, Telford W, Upadhyaya KD, Rechache K, Kanakry CG, Kanakry JA. Frequency, kinetics, and clinical significance of HHV-6 DNAemia after PTCy-based hematopoietic cell transplant. Blood Adv. 2026 Jul 17:bloodadvances.2025018166. doi: 10.1182/bloodadvances.2025018166. Online ahead of print.

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