Rapid Transport and Infusion of Hematopoietic Stem Cells Can Improve Outcome after Unrelated Donor Transplant.

Abstract

Abstract The site of collection of bone marrow (BM) or peripheral blood (PB) grafts for unrelated donor (URD) transplantation depend on the geographic location of the donor and is therefore subject to variations in transport time to transplant centers (TC). We evaluated the impact of transport and other graft characteristics that might influence outcome after transplantation. Transport factors examined include: number of collections, time from end of collection to receipt at TC, manipulation of the graft at TC and time from receipt at TC to infusion. All patients received T-replete grafts, myeloablative conditioning regimens and calcinuerin-inhibitor graft-versus-host disease prophylaxis. Collections were facilitated by the NMDP in 2000–2004 for patients with acute and chronic leukemia in 1st or 2nd remission and myelodysplastic syndrome (refractory anemia); approximately 60% of patients were in 1st remission. Median ages at transplant were 27 years for BM and 35 years for PB recipients. 115 centers collected 938 BM grafts and 80 centers, 507 PB grafts; >90% of collections occurred in the U.S. All BM grafts involved a single collection; 58% of PB grafts involved two collections. 93% of BM grafts were transported at room temperature; 98% of PB grafts were transported in a refrigerated gel-pack. Median time from collection of BM grafts to receipt at TC was 9.3 (range 0.5–46.7) hours and from receipt at TC to infusion was 3.2 (0.1–45.2) hours. Corresponding times for PB grafts were 10.4 (0.5–45.3) and 2.8 (0.1–39.1) hours. Sixty percent of BM and 19% of PB grafts were manipulated (for ABO incompatibility, plasma removal or volume reduction) at TC prior to infusion. Most patients achieved neutrophil recovery by day-28 after BM (93%) and PB (96%) transplants. No transport factors were associated with likelihood of day-28 neutrophil recovery. However, neutrophil recovery by day-28 was more likely when total nucleated cell dose of BM graft at shipping was >5 × 108/kg (odds ratio [OR] 2.74, p=0.013). A cell dose effect was not seen with PB but only 17% of PB grafts contained ≤5 × 108/kg mononuclear cells. Platelet recovery after transplantation of BM and PB grafts appeared to be influenced by time from receipt of graft at TC to infusion; infusion >6 hours after receipt was associated with a lower probability of platelet recovery (OR 0.67, p=0.021 and OR=0.58, p=0.029, respectively). The 60-day probabilities of platelet recovery when BM and PB grafts were infused ≤6 hours were 76% and 84%, respectively. Corresponding probabilities when infusion occurred >6 hours were 67% and 76%. Twenty four percent of BM and 27% of PB grafts were infused >6 hours after receipt at TC. Manipulation of the graft accounted for the delay in infusion for 167 of 228 (73%) of BM and 35 of 135 (26%) of PB transplants. Secondary graft failure rates were 9% after BM and 7% after PB transplants; a third of failures were associated with recurrent leukemia. After adjusting for other significant factors, overall mortality rates were higher when PB grafts involved 2 collections (relative risk [RR] 1.35, p=0.014) and for BM grafts, when interval from end of collection to receipt at TC was >20 hours (RR, 1.47, p=0.023). Therefore, outcomes after URD transplants for hematologic malignancies may be improved by shortening transport time for BM grafts and minimizing lag time between receipt at TC and infusion, regardless of graft type.