Volunteer Unrelated Donor PBSC Collection Efficacy and Recipient Outcomes: Results of a Prospective National Marrow Donor Program (NMDP) Trial, 1999–2003.

In spite of limited multi-institutional outcome data and concern about high rates of chronic GVHD, PBSC has become the most frequently used unrelated donor stem cell source. We present an analysis of 1178 non-T-cell depleted donor/recipient pairs enrolled on a prospective trial conducted by the NMDP (1999–2003; med f/u 762 d). Multivariate analysis revealed that younger donors, heavier donors, or donors with higher pre-apheresis CD34+ cell numbers gave significantly higher CD34+ yields. The median time to neutrophil and platelet engraftment >50K was 14 and 24 days, respectively. Recipients were more likely to have neutrophil engraftment by day 25 if the pre-BMT Karnofsky score was ≥90 (OR 0.31 for <90, p<0.001) or if the donor blood volume processed was about 24 L (OR 2.88 for 24L vs. <19L, p=0.006). Recipients were more likely to engraft platelets by day 60 if their Karnofsky score was ≥90 (OR 0.66 for <90, p=0.006), they were CMV seronegative (OR 0.66 for CMV+, p=0.004) or the number of CD34+ cells/kg recipient wt in the infused product was higher (OR 2.94 for >9.5x10⁶ CD34+ cells/kg vs <3.6, p<0.001). Surprisingly, a higher incidence of grade II-IV aGvHD at 100 days was noted in pediatric compared to adult patients (58% vs. 45%, p = 0.009), although rates of grade III-IV aGvHD were similar (31 vs. 26%, p= 0.28). Adjustment for the lower rate of reduced intensity conditioning (RIC) performed in children (15% vs. 45%) plus a higher mismatch rate (14% vs. 10%) explained some but not all of this effect (RR decreased from 1.62 to 1.29). Lower rates of grade II-IV aGVHD were also noted for HLA matched vs mismatched (45 vs. 56%, p = 0.017), and RIC vs. myeloablative patients (39 vs. 51%, p < 0.0001). FK506 was superior to CsA-based regimens in preventing grade II-IV aGvHD (RR 0.73, p=0.003). Of note, higher total WBC in the infused product was found to be associated with a lower risk of developing grade III-IV aGvHD (<45 x 10⁹ vs ≥ 91 x 10⁹, RR 0.64, p=0.009). Among 565 recipients who developed cGvHD (cumulative incidence 50% in adult and 58% in pediatric recipients at 2 yrs), 110 (19%) had limited and 455 (81%) extensive involvement. Chronic GvHD occurred more often with CsA vs. FK506 (RR 0.64 for FK506, p<0.001). An advantage in survival at one year was noted for early vs. intermediate vs. high risk disease (1yr OS 57 vs. 45 vs. 33%, p < 0.0001) and 6/6 HLA matched vs. mismatched groups (1yr OS 48 vs. 38%, p = 0.007). At latest follow up, the risk of dying was higher in recipients who had a Karnofsky score <90 (RR 1.56, p<0.001), were CMV seropositive (RR 1.23, p=0.006), had an HLA-mismatched donor (RR 1.46, p=0.001), or received a myeloablative transplant (RIC RR 0.73, p<0.001). In addition, smaller product volume or lower platelet count in the product also resulted in poorer survival (high vs. low RR of 0.70 (volume ) and 0.82 (platelets), p=0.005). In conclusion, unrelated donor PBSC results in rapid engraftment and acceptable long-term survival outcomes, but cGVHD occurs in >50% of recipients. Better outcomes are associated with use of FK-506, 24L of collection, higher product cell counts, RIC regimens, matched donors, low risk disease and high Karnofsky scores. Pediatric recipients have similar or worse GvHD outcomes compared to adults.