Allograft T cell depletion (TCD) reduces acute graft-vs. host disease (aGVHD) after myeloablative hematopoietic stem cell transplantation (HSCT). Lower incidences of aGVHD reported after reduced-intensity stem cell transplantation (RIST) may reflect delayed donor T cell engraftment. We compared the incidence of aGVHD following RIST with TCD (19 patients (pts) vs. T cell replete (TCR) allografts (20 pts)(Table). There was no difference in the incidence aGVHD, occurring in 71% of TCD recipients (median onset Day 47) and 70% of TCR recipients (median onset Day 25). After TCD, 100% of those who engrafted prior to any DLI developed aGVHD compared with 56% of those who engrafted after DLI, including two pts who developed “late-acute” aGVHD after Day 100, upon completion of donor T cell engraftment. T cell engraftment after TCD was uneven: engraftment kinetics were associated with residual host circulating CD8+ T cell counts after immune depletion; and aGVHD did not occur in the setting of mixed T cell chimerism (Figure). These observations demonstrate that aGVHD can occur with very low doses (105/kg) of allograft T cells after RIST. Protection from aGVHD conferred by mixed T cell chimerism may be lost with full donor T cell engraftment. With limited donor T cell numbers, host T cells appear to determine kinetics of engraftment and of aGVHD after RIST. Figure:

  • Post-induction circulating CD8+ T cell counts in TCD recipients with delayed donor T cell engraftment.

  • After TCD, all subjects who developed aGVHD did so at or after the establishment of T cell full donor T cell chimerism, and occasionally prior to any DLI.

Shaded triangle represents the theoretical area in which values would fall if subjects developed aGVHD prior to complete donor T cell engraftment. Arrows: DLI.

Patient and Transplant Characteristics and Outcomes

ProtocolTCDTCR
Flu/Cy: Fludarabine and cyclophosphamide; EPOCH-F: Etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone and fludarabine; FDC: Full donor chimerism. 
 Median (range) Median (range) 
Recipient Age 43 years (32 – 56) 44 (19 – 67) 
CMV Risk 14/19 16/20 
Pretransplant Immune Depletion Flu/Cy EPOCH-F 
Conditioning Regimen Flu/Cy Flu/Cy 
Pre-conditioning Host Cell Counts:  
CD3 86 (1 – 701) 140 (21 – 441) 
CD4, p=0.017 44 (1 – 156) 71 (12 – 191) 
CD8 34 (0 – 555) 55 (2 – 309) 
NK 58 (0 – 376) 88 (3 – 467) 
Day 0 CD3 Cell Count 1 (1 – 6) 5 (0 – 42) 
Allograft CD34+ cells/kg 7.75 x 106 (5.1 – 12.9) 7.68 x 106 (4.6–18.4) 
Allograft CD3+ cells/kg 1.0 x 105 (preset) 3.63 x 108 (1.5 – 8.3) 
Donor T cell engraftment Day +70 (14 – 180) 14 (14 – 100) 
ProtocolTCDTCR
Flu/Cy: Fludarabine and cyclophosphamide; EPOCH-F: Etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone and fludarabine; FDC: Full donor chimerism. 
 Median (range) Median (range) 
Recipient Age 43 years (32 – 56) 44 (19 – 67) 
CMV Risk 14/19 16/20 
Pretransplant Immune Depletion Flu/Cy EPOCH-F 
Conditioning Regimen Flu/Cy Flu/Cy 
Pre-conditioning Host Cell Counts:  
CD3 86 (1 – 701) 140 (21 – 441) 
CD4, p=0.017 44 (1 – 156) 71 (12 – 191) 
CD8 34 (0 – 555) 55 (2 – 309) 
NK 58 (0 – 376) 88 (3 – 467) 
Day 0 CD3 Cell Count 1 (1 – 6) 5 (0 – 42) 
Allograft CD34+ cells/kg 7.75 x 106 (5.1 – 12.9) 7.68 x 106 (4.6–18.4) 
Allograft CD3+ cells/kg 1.0 x 105 (preset) 3.63 x 108 (1.5 – 8.3) 
Donor T cell engraftment Day +70 (14 – 180) 14 (14 – 100) 
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Topics:
allografting, graft-versus-host disease, hematopoietic stem cell transplantation, t-lymphocytes, influenza, radioimmunosorbent test, brachial plexus neuritis, cyclophosphamide, epoch protocol, fludarabine

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2006, The American Society of Hematology
2006
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