Engraftment and Survival Following Non-Myeloablative Allogeneic Peripheral Blood Hematopoietic Cell Transplantation for Malignant Diseases Is Affected by CD8⁺ T-Cell Dose.

The influence of graft composition on clinical outcomes after non-myeloablative allogeneic hematopoietic transplantation is not well characterized. In this report we evaluated the influence of CD34⁺, CD3⁺, CD4⁺, and CD8⁺ cell doses on donor engraftment, graft-versus-host disease (GVHD), freedom from progression (FFP), and overall survival (OS). Patients (n=63) were given total body irradiation 200 cGy (n=8) or total body irradiation 200 cGy plus fludarabine (n=55) followed by allografting with granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC). The median age was 53 years, and donors were HLA-identical siblings (n=38) or HLA-matched unrelated individuals (n=25). Almost all patient were treated for a hematologic malignancy (n=60), with 30 patients (48%) characterized as having advanced diseases. G-PBMC cell doses were prospectively enumerated by FACS analysis at the time of collection. Median donor G-PBMC cell doses were 7.4x10⁶ CD34⁺/kg (range: 1.9–17.7), 3.2x10⁸ CD3⁺/kg (range: 0.8–6.4), 2.1x10⁸ CD4⁺/kg (range: 0.4–4.1), and 1.1x10⁸ CD8⁺/kg (range: 0.2–3.4). By univariate analysis only G-PBMC CD8⁺ T-cell dose ≥ the 50^th percentile favorably correlated with attainment of full donor blood T-cell chimerism (P = .03). The incidences of grade 2–4 acute GVHD was 16.3% (95% CI: 6.9–25.8) and extensive chronic GVHD was 42.9% (95% CI: 27.8–57.9). No G-PBMC cell dose significantly influenced grade 2–4 acute or extensive chronic GVHD. With a median follow-up of 13 months (range: 5–45), estimates for FFP was 53.7% (95% CI: 37.7–69.7) and OS was 33.4% (95% CI: 17.4–49.4). G-PBMC CD8⁺ T-cell dose ≥ the 50^th percentile T-cell dose was favorably prognostic for both FFP (P = .001) and OS (P = .01). Survival curves for FFP and OS are shown in Figure 1. Extensive chronic GVHD also predicted better FFP (P = .02), but in multivariate analysis only G-PBMC CD8 ⁺ T-cell dose (P = .004; RR = 0.2, 95% CI = 0.1–0.6) was associated with improved FFP. Infusion of low G-PBMC CD8⁺ T-cell dose for non-myeloablative allografting with total body irradiation 200 cGy plus fludarabine may adversely affect donor T-cell engraftment, disease progression and survival outcomes.

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