ArticleBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2017
Mixed T Cell Chimerism After Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using an Alemtuzumab-Containing Regimen Is Shaped by Persistence of Recipient CD8 T Cells.
Article in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Guideline
- Article
- Acquired Aplastic Anemia Therapies: Immunosuppressive Therapy Versus Alternative Donor Hematopoietic Cell Transplantation.Journal of hematology · 2024Review
- The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults.Frontiers in immunology · 2024Review
- Long-Term Mixed Chimerism AfterFrontiers in oncology · 2021Article
- Natural Barcodes for Longitudinal Single Cell Tracking of Leukemic and Immune Cell Dynamics.Frontiers in immunology · 2021Review
- Postvaccination graft dysfunction/aplastic anemia relapse with massive clonal expansion of autologous CD8+ lymphocytes.Blood advances · 2020Article
- Autoimmune cytopenias (AIC) following allogeneic haematopoietic stem cell transplant for acquired aplastic anaemia: a joint study of the Autoimmune Diseases and Severe Aplastic Anaemia Working Parties (ADWP/SAAWP) of the European Society for Blood and Marrow Transplantation (EBMT).Bone marrow transplantation · 2020Article
- Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years.Blood advances · 2019Article
- Transplant-Associated Thrombotic Microangiopathy in Pediatric Hematopoietic Cell Transplant Recipients: A Practical Approach to Diagnosis and Management.Frontiers in pediatrics · 2019Review
- Differential Interaction of Peripheral Blood Lymphocyte Counts (ALC) With DifferentFrontiers in oncology · 2019Article
- Diagnosis and Treatment of Aplastic Anemia.Current treatment options in oncology · 2017Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90.7%. Acute and chronic GVHD each occurred in 6 patients (13.3%), and only 1 case was severe. Mixed T cell chimerism was frequent and persisted after cessation of immunosuppression. T cells were extensively depleted, representing only 11.3% of lymphocytes at day 30 and rising to 43.8% by 1 year, but still significantly below normal levels (67.2%; P = .018), and deficiency persisted after immunosuppressive therapy (IST) withdrawal. Depletion of CD4 T cells was particularly profound, causing inversion of the normal CD4:CD8 T cell ratio. T cell subset composition was also abnormal, with memory and effector T cells predominating for at least 6 months after FCC HSCT. Analysis of T cell subset chimerism showed that CD4 T cells were predominantly donor-derived at 1 year, whereas recipient-derived CD8 T cells shaped mixed chimerism with a notable contribution of recipient effector CD8 T cells. The prolonged mixed T cell chimerism after IST withdrawal and low incidence of GVHD indicates the establishment of mutual tolerance, but the low incidence of viral disease suggests maintenance of antiviral immunity. Our study shows that despite the abnormal T cell profile after allogeneic HSCT for SAA using the FCC regimen, this regimen is conducive to an excellent clinical outcome.
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