Second Transplant with HLA Haplo-Identical Hematopoietic Stem Cells for Graft Failure after Double Units Cord Blood Transplantation.
Authors: Yao Wen , Sun Zimin , Liu Huilan , dortor Xingbing Wang , Wsng Zuyi , Yuan Xiao 
Published: October 2019

Abstract
Graft failure (GF) can be a fatal complication following cord blood transplantation (CBT). Up to date, there has not been an ideal treatment for it. Recently, second transplant has been used as a potential therapy for treatment of GF. However, it is unclear which is the best source for donor cells that result successful engraftment and low rate of complications related to transplantation. In this study, we evaluated the outcomes and safety of second transplant with HLA haplo-identical hematopoietic stem cells for graft failure after double units cord blood transplantation in three patients. These patients suffered from myelodysplasia (MDS), acute lymphoblastic leukemia (ALL), severe aplastic anemia (SAA) respectively (median age, 16 years; range, 10–20 years). After myeloablative conditioning, all of them received double umbilical cord blood (UCB) units with at least one 5/6 HLA-matched unit (median infused dose, 6.85×107 nucleated cell [NC]/kg; range, 6.28–7.17×107 NC/kg). The characteristics of these patients and double cord blood transplantation data are detailed in the following Table. The former two patients developed early GF on 30 days after CBT. In the third patient, neutrophil and platelet recovery was observed on +14d and +31d respectively, and sustained hamatopoiesis was derived from a single donor with higher nucleated and CD34+ cells until 4 months after CBT when late GF happened, After reduced-intensity or myeloablative conditioning, all of them subsequently received HLA haplo-identical three-loci mismatched HSCT donated by their mothers (median infused dose, 8.40×108 nucleated cell [NC]/kg; range, 8.02–9.82×107 NC/kg). The time interval from GF to the second transplantation of these patients ranged from 7 to 10 days. Cyclosporine A (CsA) and mycophenolate mofetil (MMF) were ad- ministered for the prophylaxis of graft-versus-host disease (GVHD). Detailed data of the second transplantation were also shown below. Engraftment was achieved on all three patients between the twelfth day and the fourteenth day after the transplantation with a full donor chimaerism. Acute GVHD of grades I–II and slight chronic GVHD occurred in these patients. All three patients survive up till now, and one patient has survived for 15 months after the second transplantation. This is the first report in china using HLA haplo-identical HSCT to rescue the GF after double CBT in China. The results are encouraging though the number of the patients is too small.
Patients’characteristics and transplantation data Patients No. 1 No. 2 No. 3 Age(years)/sex 20/F 10/M 16/F Body weight 43.5kg 32kg 40kg Diagnosis MDS ALL(CR1) SAA Conditioning Ara-c/CY/TBI BU/CY CY/ATG Nucleated cells (CB1/CB2) (4.02/2.83)×107/kg (3.92/2.36)×107/kg (2.44/4.73)×107/kg CD34+ cells (CB1/CB2) (0.61/0.28)×105/kg (2.55/0.85)×105/kg (0.53/1.42)×105/kg CD3+ cells (CB1/CB2) (2.26/2.34)×106/kg (0.37/0.16)×106/kg (0.53/0.35)×106/kg HLA-mismatched (CB1; CB2) 2/6; 1/6. 1/6; 0/6 0/6; 1/6 GF 30d 30d 4m Second transplant 37d 38d 4m Conditioning Flu/ATG TBI2GY/ATG Flu/CY/ATG GVHD prhphylaxis CsA+MMF CsA+MMF CsA+MMF Nucleated cells 8.02×108/kg 8.40×108/kg 9.82×108/kg CD34+ cells 4.31×106/kg 3.50×106/kg 7.86×106/kg ANC>0.5×109/L 12d 13d 14d PLT>2×109/L 18d 17d 18d Follow up 15M+ 3M+ 12M+