Ex-Vivo Reduction of Allograft T Cell Dose Does Not Prevent Acute Graft-vs-Host Disease after Reduced-Intensity Hematopoietic Stem Cell Transplantation

• Published in: Blood 2006-11, Vol.108 (11), p.2871-2871
• Main Authors: Hardy, Nancy M., Hakim, Frances, Steinberg, Seth, Krumlauf, Michael, Babb, Rebecca, Odom, Jeanne, Fowler, Daniel, Gress, Ronald, Bishop, Michael R.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V108.11.2871.2871

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 OutcomesProtocolTCDTCRMedian (range)Median (range)Recipient Age43 years (32 – 56)44 (19 – 67)CMV Risk14/1916/20Pretransplant Immune DepletionFlu/CyEPOCH-FConditioning RegimenFlu/CyFlu/CyPre-conditioning Host Cell Counts:CD386 (1 – 701)140 (21 – 441)CD4, p=0.01744 (1 – 156)71 (12 – 191)CD834 (0 – 555)55 (2 – 309)NK58 (0 – 376)88 (3 – 467)Day 0 CD3 Cell Count1 (1 – 6)5 (0 – 42)Allograft CD34+ cells/kg7.75 x 106 (5.1 – 12.9)7.68 x 106 (4.6–18.4)Allograft CD3+ cells/kg1.0 x 105 (preset)3.63 x 108 (1.5 – 8.3)Donor T cell engraftmentDay +70 (14 – 180)14 (14 – 100)Flu/Cy: Fludarabine and cyclophosphamide; EPOCH-F: Etoposide, doxorubicin, vincristine, cyclophospha