Transplantation of Multiple Cord Blood Units for Patients with Hematologic Malignancy.
Authors: Sun Zimin , Liu Huilan , Geng Liangquan , Liu Xin , Yang Huizhi , Wang Zuyi 
Published: October 2019

Limited number of umbilical cord blood (UCB) cells indeed compromises the result of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety and effectiveness of the combined transplantation of multiple partially HLA-match UCB units which was scarcely performed in china. After myeloablative conditioning, six patients with high-risk hematologic malignancy (median age, 29 years; range, 10–37 years) received two or three UCB units with at least one 5/6 HLA-match unit (median infused dose, 3.77×107 nucleated cell [NC]/kg; range, 3.40–7.49×107 NC/kg). Patients’ characteristics and transplantation data are detailed in Table 1. Five patients were engrafted successfully at a median of 22 days (range, 16–29 days) except one patient developed early graft failure (GF). In one patient, engraftment was derived from both donors for six months until her death. The both units’ were 6/6 HLA-A-, HLA-B-, and HLA-DRB1- matched the recipient’s, and they had similar number of nucleated cells, CD34 positive cells and CD3 positive cells. In the remaining four patients, Sustained hamatopoiesis was derived from a single donor which predominated as early as the day of engraftment after hematopoietic stem cell transplantation (HSCT). Units with a higher number of total nucleated cells and CD34+ cells predominated in two and one of four patients, respectively, and units with higher numbers of CD3+ cells predominated in three of four patients. The degree of HLA mismatch is also important (Table 2). Acute GVHD grades I-II was observed in the five patients. Two of them died of invasive fungus infection, one died of serious hepatitis, the remaining two patients were both alive and one survived in continuous complete remission 6 months after HSCT. Therefore, transplantation of multiple partly HLA-matched UCB units is a promising procedure to overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents.

Patient characteristics and transplantation data Patients No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Age(years)/sex 37/F 30/M 32/M 27/M 10/M 10/F Body weight 64kg 84kg 69.5kg 56kg 32kg Diagnosis ALL ALL(Ph+) ANLL(M0) ALL ALL(Ph+) ANLL(M2) Pre-CBT status CR2 CR2 CR1 CR1 CR1 CR1 Conditioning TBI12GY/Ara-c/CY TBI12GY/Ara-c/CY TBI12GY/Ara-c/CY TBI12GY/Ara-c/CY BU/CY BU/CY/ATG Nucleated cells 3.51×107/kg 3.40×107/kg 3.43×107/kg 4.03×107/kg 6.28×107/kg 7.49×107/kg CD34+ cells 2.37×107/kg 2.75×105/kg 4.28×105/kg 2.22×105/kg 3.40×105/kg 5.51×105/kg ANC>0.5×109/L 21d 27d 16d 29d No 22d Plt>20×109/L 30d No No 46d No 30d Over survive 6M 60d 94d 4M+ 2M+ 1M+ Outcomes Death(hepatitis) Death(IFI) Death(IFI) Live GF Live Characteristics of dominant and non-dominant cord blood units Patients No. 2 No. 3 No. 4 No. 6 Nucleated cells(×107/kg) Dominant unit 1.14 1.88 1.33 3.79 Non-dominant unit1 0.94 1.55 1.45 3.7 Non-dominant unit2 1.32 CD34+ cells(×105/kg) Dominant unit 0.81 1.56 1.45 1.86 Non-dominant unit1 0.76 2.72 0.77 3.29 Non-dominant unit2 1.18 CD3+ cells(×107/kg) Dominant unit 0.27 0.53 0.42 0.68 Non-dominant unit1 0.14 0.4 0.34 0.63 Non-dominant unit2 0.34 Seratype (HLA-A,-B) and low-resolusion genotype (HLA-DR) mismatch Dominant unit 1/6. 1/6. 1/6. 0/6. Non-dominant unit1 1/6. 1/6. 1/6. 1/6. Non-dominant unit2 1/6.