Clinical Outcome of Hematopoietic Stem Cell Transplantation (HSCT) Using Plasma Depleted Umbilical Cord Blood Units (UCB) That Were Not Depleted of Red Blood Cells Prior to Cryopreservation.

Background: UCB is an attractive source for HSCT because of less stringent HLA matching requirements, lower incidence and severity of GvHD, and ready availability of a physical inventory. However, unlike BMT or PSCT, the limiting cell dose associated with UCB units has hampered its widespread use. The red cell depletion (RCD) techniques that are widely used by UCB banks incur significant nucleated cell loss after processing. One method of minimizing cell loss during processing is to deplete plasma (PD) but not red blood cells. A large racially diverse inventory of 18,000 PD UCB is now available on stem cell registries; however, clinical outcome for HSCT using PD UCB products is unavailable.

Hypothesis: Usage of PD UCB in unrelated HSCT will result in acceptable clinical outcome for myeloid (ANC 500) and platelet engraftment, overall survival (OS), event-free-survival (EFS), and transplant related mortality (TRM).

Methods: A retrospective analysis limited to patients without prior transplants and transplanted during remission (“eligible”) was performed on 98 HSCT using PD UCB. An additional 20 “high risk” patients with prior transplants or transplanted during relapse were included in the engraftment and survival analysis.

Results: Average loss of less than 0.1% nucleated cells was found in the discarded plasma fraction after PD UCB processing (n=27), though cell clumping limited the cellular fraction recovery to 90%. Outcome on engraftment and/or survival was available for 98 patients (median age 6.7 yo, range 0.3–54 yo, 24 >16 yo; median weight 23.5 kg, range 4.5–88 kg, 27 >50kg; male 60%; median # HLA ABDR matches 4.0; median pre-freeze TNC dose 5.7 x 10⁷/kg; transplant center reported median post-thaw TNC dose 5.5 x 10⁷/kg; median pre-freeze CD34 dose 2.0 x 10⁵/kg; malignant indications 71%; transplants outside U.S. 37%; double unit transplant 14%; and non-myeloablative 7%). The median time to engraftment for ANC 500 (n=87), platelet 20K (n=72) and 50K (n=68) were 22.0 days (range 7–49 days), 49.5 days (range 13–94 days), and 58.0 days (range 21–132 days) respectively. The unadjusted cumulative incidence of ANC500 and platelet 20K and 50K engraftment were 94±3%, 81±5% and 80±5% respectively for 98 eligible patients, and 90±3%, 77±5% and 75±5% respectively for the eligible plus high risk patients. The incidence of grade III–IV acute GVHD and extensive chronic GVHD were 15% and 14% respectively. Relapse rate for malignancies (n=67) and TRM (n=98) were 20±6% and 20±4% respectively at 1 year. With a median follow-up of 297 days (range 50–1,263 days), the Kaplan-Meier estimates of 1-year survival (n=98) and disease-free survival (n=67) are 73±5% and 59±7% respectively for the eligible patients, and 65±5% (n=118) and 50±6% (n=85) respectively for the eligible plus high risk patients.

Conclusion: These results demonstrate that HSCT using PD UCB can be performed safely and effectively.