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.
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.
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Medicine, Haematology Division, AOU Federico II, Naples, Italy.
Francesco
F
Grimaldi
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Victoria
V
Potter
Division of Cancer Studies, King's College London, London, United Kingdom.
Pilar
P
Perez-Abellan
Division of Cancer Studies, King's College London, London, United Kingdom.
John P
JP
Veluchamy
Division of Cancer Studies, King's College London, London, United Kingdom.
Muhammad
M
Atif
Division of Cancer Studies, King's College London, London, United Kingdom.
Rosemary
R
Grain
Division of Cancer Studies, King's College London, London, United Kingdom.
Monica
M
Sen
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Steven
S
Best
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Nicholas
N
Lea
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Carmel
C
Rice
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Antonio
A
Pagliuca
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom; Division of Cancer Studies, King's College London, London, United Kingdom.
Ghulam J
GJ
Mufti
Department of Haematology, King's College Hospital NHS Foundation Trust, London, United Kingdom; Division of Cancer Studies, King's College London, London, United Kingdom. Electronic address: judith.marsh@nhs.net.
Judith C W
JCW
Marsh
Division of Cancer Studies, King's College London, London, United Kingdom. Electronic address: linda.barber@kcl.ac.uk.
Linda D
LD
Barber
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab / Q000494:pharmacology*; D000741:Anemia, Aplastic / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014916:Whole-Body Irradiation; D055815:Young Adult
D007166:Immunosuppressive Agents; D000074323:Alemtuzumab
Alemtuzumab; Aplastic anemia; Chimerism; Hematopoietic stem cell transplantation; T cells