1. 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
- Author
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Grimaldi, Francesco, Potter, Victoria, Perez-Abellan, Pilar, Veluchamy, John P., Atif, Muhammad, Grain, Rosemary, Sen, Monica, Best, Steven, Lea, Nicholas, Rice, Carmel, Pagliuca, Antonio, Mufti, Ghulam J., Marsh, Judith C.W., and Barber, Linda D.
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Adult ,Male ,Transplantation Conditioning ,Adolescent ,aplastic anemia ,Cell Survival ,education ,T cells ,Hematopoietic stem cell transplantation ,CD8-Positive T-Lymphocytes ,Chimerism ,Article ,Young Adult ,T-Lymphocyte Subsets ,alemtuzumab ,Humans ,Alemtuzumab ,Retrospective Studies ,Transplantation ,Transplantation Chimera ,Graft Survival ,Anemia, Aplastic ,Hematology ,Middle Aged ,humanities ,Treatment Outcome ,surgical procedures, operative ,chimerism ,hematopoietic stem cell transplantation ,Female ,Aplastic anemia ,Immunosuppressive Agents ,Whole-Body Irradiation - Abstract
Highlights • Clinical outcomes are excellent using an alemtuzumab-containing hematopoietic stem cell transplantation regimen for aplastic anemia. • Outcomes are excellent despite prolonged abnormality of the T cell profile. • Recipient-derived CD8 T cells shape persistent mixed chimerism., 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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