Hematopoietic Stem Cell Transplantation (HSCT) for Benign Indications Using Umbilical Cord Blood Units (UCB) That Were Depleted of Plasma, but Not of Red Blood Cells.

Background: UCB is an attractive unrelated source for HSCT of benign indications such as hemoglobinapathies, genetic diseases and metabolic disorders, 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, cell dosage is a critical factor in success of UCB HSCT. 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, but not the red blood cells (PD). A large racially diverse PD UCB inventory of 18,000 units is now available on stem cell registries. We now report our observations of using unrelated PD UCB HSCT for benign indications.

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

Methods: A retrospective analysis was performed on 28 patients with benign disorders who were transplanted with PD UCB in 15 centers and 7 countries, with 13 thalassemias, 5 SAA, 5 WAS, 2 SCID, 1 sickle cell disease, 1 osteopetrosis and 1 metabolic disorder.

Results: The median age of patients was 3.7 years old (range 03–27 years old); median weight 16.0 kg (range 4.5–43 kg); male 57%. Transplant characteristics indicated a median # HLA ABDR matches of 4.0 (5 6/6; 7 5/6; 12 4/6; 3 3/6; 1NA); median pre-freeze TNC dose 7.7 x 10⁷/kg; median post-thaw TNC dose as reported by TC 7.7 x 10⁷/kg; median pre-freeze CD34 dose 3.1 x 10⁵/kg; transplants performed outside of U.S. 68%; double unit transplant 13%; non-myeloablative 6%. The median time to engraftment for ANC 500 (n=21), platelet 20K (n=20), and 50K (n=18) are 14.5 days (range 11–41 days), 47.0 days (range 13–82 days), and 55.0 days (range 21–96 days) respectively. The unadjusted cumulative incidence (C.I.) of ANC500 and platelet 20K and 50K engraftment are 89±7%, 89±7%, and 87±8% respectively. The incidence of reported grade II–IV acute GVHD was 33%, and none had grade III–IV acute GVHD. 50% developed limited chronic GVHD (7/14), and so far only one patient was reported to have extensive chronic GVHD. With a median follow-up of 356 days (range 93–1,100 days), the Kaplan-Meier estimates of 1-year TRM, OS and disease-free survival were 11±6%, 89±6% and 89±6% respectively.

Conclusion: These results demonstrate that HSCT using unrelated PD UCB can be performed safely and effectively in patients with benign disorders. Further study of HSCT using unrelated PD UCB in patients with non-malignant hematological disorders is warranted.