Median Number Of Total Nucleated Cells Research Articles

Better Engraftment of Single-Unit Unrelated Cord Blood Transplantation in Patients with Acquired Severe Aplastic Anemia Not Respond to IST Using Conditioning Regimen without ATG

Background: Previous studies show that the use of single-unit unrelated cord blood transplantation (sUCBT) for severe aplastic anemia (SAA) has poor outcome because of high incidence of primary graft failure. Effective measures to completely prevent rejection in SAA remain to be identified, but higher cell dose, less HLA disparities and better conditioning regimen are known to improve the outcome. In this study we compare two conditioning regimens to determine which is better to facilitate engraftment after sUCBT. Patients and methods: We retrospectively analyzed the outcomes of 21 Chinese patients with acquired SAA who do not have HLA-matched siblings and do not respond to first-line immunosuppressive therapy with ciclosporin (CSA) and/or anti-thymocyte globulin (ATG) that received sUCBT were included beteween July 2016 and October 2018. Data collected as of June 2019 were analyzed. 6 patients (ATG group) used a conditioning regimen consisting of ATG (rabbit) 2.5 mg/kg (D-9 to D-7) with fludarabine 30 mg/m2 (D-9 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (3 Gray) on D-1. Median age at time of sUCBT was 11 (5-20) years, median body weight was 34(18-53)kg. Waiting time from diagnosis to transplantation was 427(277-3407)days. The median total nucleated cell number and CD34-positive cell number at infusion were 3.57(2.77-9.36) × 107/kg and 2.5(1.02-3.99) × 105/kg, respectively. Another group (No-ATG) of 15 patients used a conditioning regimen without ATG consisting of fludarabine 40 mg/m2 (D-8 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (4 Gray) on D-1. Median age at time of UCBT was 11 (3-42) years, median body weight was 35(13-70)kg. Waiting time from diagnosis to transplantation was 1664(160-2006)days. The median total nucleated cell number and CD34-positive cell number at infusion were 3.63(1.65-9.38)×107/kg and 2.5(0.69-5.61)×105/kg, respectively. CsA and MMF was given to both groups as prophylaxis for graft versus host disease (GVHD). Results: Primary graft failure was observed in 4 out of 6 patients in ATG group. All of these 4 patients received salvage transplantation with haploidentical related donor, 3 patients died after salvage transplantation due to grade IV GVHD in intestinal tract and infection. However, all of 15 patients in the No-ATG group had completely engraftment. The median time to neutrophil engraftment was 18 (13-27) days, platelet engraftment was 32 (17-112) days. 42-day cumulative incidence of engraftment is 100% compared to 33% in ATG group (P=0.008). During follow-up, 2 patients died before 1 year due to renal failure (n=1) and encephalorrhagia (n=1) in the No-ATG group. One-year survival rate is 86.7% in No-ATG group compared to 50% in ATG group (P=0.0598). Conclusion: sUCBT after a FLU-CY-TBI conditioning regimen was an effective and safe option for SAA patients, with better engraftment and survival. Pediatric and adult SAA patients who are younger than 50 years old, lack of HLA-matched sibling donor and refractory to immunosuppressive therapy should consider sUCBT. Table Disclosures No relevant conflicts of interest to declare.

Combination of a Cyclophosphamide-Total Body Irradiation Conditioning Regimen and Tacrolimus Plus Mycophenolate Mofetil for Gvhd Prophylaxis Is Associated with Higher HHV-6 Encephalitis Incidence after Cord Blood Transplantation

Background Human herpesvirus-6 (HHV-6) encephalitis occurs frequently through cord blood transplantation (CBT), and leads to a high risk of mortality and morbidity. Although CBT is a known risk factor for HHV-6 encephalitis, a thorough analysis of risk factors for HHV-6 encephalitis in patients receiving CBT has not been performed, and several risk factors remain unidentified. In our center, generally, either tacrolimus (Tac) plus methotrexate (MTX) (Tac/MTX) or mycophenolate mofetil (MMF) (Tac/MMF) was selected for graft-versus-host disease (GVHD) prophylaxis after CBT, at the physician's discretion. However, in recent years, Tac/MMF became the standard choice. We observed that the incidence of HHV-6 encephalitis tended to be markedly higher among patients receiving treatment with a cyclophosphamide (Cy) and total body irradiation (TBI) (Cy/TBI)-based regimen and Tac/MMF after CBT. Therefore, we aimed to ascertain whether certain conditioning regimens and GVHD prophylaxis regimens are associated with the occurrence of HHV-6 encephalitis after CBT. Methods In this retrospective study, we examined 103 patients undergoing CBT for hematological diseases at our center between 2011 and 2019. To analyze the effect of GVHD prophylaxis on the occurrence of HHV-6 encephalitis, we divided patients into two groups based on the GVHD prophylaxis regimen used: the Tac/MTX group and the Tac/MMF group. We excluded one patient who received Tac alone and one who received cyclosporine plus MTX. Finally, 101 patients were enrolled. Routine peripheral blood examinations for HHV-6 were performed once or twice a week. HHV-6 encephalitis was defined as the presence of a central nervous system dysfunction, along with a positive polymerase chain reaction result for HHV-6 DNA in the cerebrospinal fluid. HHV-6 viremia was defined as the presence of HHV-6 in the peripheral blood. Results The median age of patients was 47 years, and the median follow-up duration for surviving patients was 432 days. Conditioning regimens included myeloablative conditioning (MAC, n=64) and reduced-intensity conditioning (RIC, n=37). MAC included Cy/TBI-based regimens in 42 patients and fludarabine (Flu) plus busulfan (Bu) (Flu/Bu)-based regimens in 23, and RIC included Flu plus melphalan-based regimens in 34 patients and other regimens in 2. Sixty-four patients received Tac/MMF as GVHD prophylaxis, whereas 37 received Tac/MTX. Six patients received HLA-matched (6/6) cord blood (CB), 27 received HLA one-antigen mismatched CB, and 68 received HLA two-antigen mismatched CB. The median total nucleated cell number and CD34-positive cell number at cryopreservation were 2.2 × 107/kg and 0.7 × 105/kg, respectively. Thirteen patients (12.8%) experienced primary graft failure. Overall, the cumulative incidence of HHV-6 viremia on day 40 was 68%, and the median time from CBT to HHV-6 viremia was 23 days. The cumulative incidence of HHV-6 viremia was significantly higher in the Tac/MMF group than in the Tac/MTX group (Tac/MMF group, 75%; Tac/MTX group, 56%; p=0.03). Ten patients developed HHV-6 encephalitis. Overall, the cumulative incidence of HHV-6 encephalitis on day 60 was 10.1%. The cumulative incidence of HHV-6 encephalitis tended to be higher in the Tac/MMF group than in the Tac/MTX group (14.1% vs. 2.7%, respectively; p=0.08). Therefore, the administration of Tac/MMF as GVHD prophylaxis after CBT was identified as a probable risk factor for HHV-6 encephalitis, and we sought to identify more such risk factors, specifically among patients receiving Tac/MMF. In the analysis of Tac/MMF group, the cumulative incidence of HHV-6 encephalitis was significantly higher among patients receiving Cy/TBI-based regimens than among those receiving other regimens (35.7% vs. 8.1%, respectively; p<0.01) (Fig. 1a). In addition, among the entire group of patients receiving Cy/TBI-based regimens, the cumulative incidence of HHV-6 encephalitis was significantly higher in the Tac/MMF than in the Tac/MTX group (35.7% vs. 0%, respectively; p<0.01) (Fig. 1b). Conclusion Our analysis showed that patients receiving Tac/MMF as GVHD prophylaxis after CBT with a Cy/TBI-based regimen have a significantly higher risk of developing HHV-6 encephalitis. Further studies using a large cohort are required to elucidate the association between the occurrence of HHV-6 encephalitis and the use of Tac/MMF in patients undergoing CBT with a Cy/TBI-based regimen. Disclosures No relevant conflicts of interest to declare.

PS1557 EARLY ENGRAFTMENT OF UNRELATED CORD BLOOD TRANSPLANTATION IN PATIENTS WITH ACQUIRED SEVERE APLASTIC ANEMIA USING CONDITIONING REGIMEN WITHOUT ANTI‐THYMOCYTE GLOBULIN

Background:Previous studies show that the use of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA) has poor outcome because of high incidence of primary graft failure. Effective measures to completely prevent rejection in SAA remain to be identified, but higher cell dose, less HLA disparities and better conditioning regimen are known to improve the outcome.Aims:In this study we compare two conditioning regimens to determine which is better to facilitate early engraftment after UCBT.Methods:We retrospectively analyzed the outcomes of 35 Chinese patients with acquired SAA who received UCBT since September 2016. 18 patients (ATG group) used a conditioning regimen consisting of ATG (thymoglobulin) 2.5 mg/kg (D‐9 to D‐7) with fludarabine 30 mg/m2 (D‐9 to D‐4), cyclophosphamide 60 mg/kg (D‐3 to D‐2) and total body irradiation (3 Gray) on D‐1. Median age at time of UCBT was 9 (4–37) years. The median total nucleated cell number and CD34‐positive cell number at infusion were 4.08 (1.74–9.36) × 107/kg and 2.13 (0.67–4.29) × 105/kg, respectively. Another group (No‐ATG) of 17 patients used a conditioning regimen without ATG consisting of fludarabine 40 mg/m2 (D‐8 to D‐4), cyclophosphamide 60 mg/kg (D‐3 to D‐2) and total body irradiation (4 Gray) on D‐1. Median age at time of UCBT was 14 (4–52) years. The median total nucleated cell number and CD34‐positive cell number at infusion were 3.5 (1.07–7.87) × 107/kg and 1.7 (0.69–5.27) × 105/kg, respectively. Ciclosporin (CsA) and mycophenolate mofetil (MMF) was given to both groups as prophylaxis for graft versus host disease (GVHD)Results:Neutrophil recovery (>0.5 × 109/L) was observed in 11 patients of the ATG group and the median time to engraftment was 19 (13–35) days. The median time to platelet recovery (>20 × 109/L) was 40 (24–153) days. Primary graft failure was observed in seven patients. Only 1 out of 17 patients in the No‐ATG group had primary graft failure. The median time to neutrophil engraftment was 17 (13–36) days. The median time to platelet engraftment was 31 (17–65) days. During follow‐up, 7 patients died before 1 year due to non‐engraftment (n = 4), infection (n = 2) and encephalorrhagia (n = 1) in the ATG group. Four patients died in the No‐ATG group due to infection (n = 3) and IV grade acute GVHD in the skin and the intestinal tract (n = 1, induced by discontinuing medicine). Furthermore, conditioning regimen without ATG shows even more superiority in patients refractory to immunosuppressive therapy with ATG and/or CsA (n = 8), who had neutrophil engraftment completely within 20 days after cord blood infusion.Summary/Conclusion:UCBT after a FLU‐CY‐TBI conditioning regimen without ATG for SAA patients is better than that with ATG, especially for patients refractory to immunosuppressive therapy. Pediatric and adult SAA patients who are younger than 50 years old, lack of HLA‐matched sibling donor and refractory to immunosuppressive therapy should consider UCBT.

Early Engraftment of Unrelated Cord Blood Transplantation in Patients with Acquired Severe Aplastic Anemia Using Conditioning Regimen without Anti-Thymocyte Globulin

Background:Previous studies show that the use of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA) has poor outcome because of high incidence of primary graft failure. Effective measures to completely prevent rejection in SAA remain to be identified, but higher cell dose, less HLA disparities and better conditioning regimen are known to improve the outcome. In this study we compare two conditioning regimens to determine which is better to facilitate early engraftment after UCBT.Patients and methods:We retrospectively analyzed the outcomes of 35 Chinese patients with acquired SAA who received UCBT since September 2016. Eighteen patients (ATG group) used a conditioning regimen consisting of ATG (thymoglobulin) 2.5 mg/kg (D-9 to D-7) with fludarabine 30 mg/m2 (D-9 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (3 Gray) on D-1. Median age at time of UCBT was 9 (4-37) years. The median total nucleated cell number and CD34-positive cell number at infusion were 4.08 (1.74-9.36) × 107/kg and 2.13 (0.67-4.29) × 105/kg, respectively. Another group (No-ATG) of 17 patients used a conditioning regimen without ATG consisting of fludarabine 40 mg/m2 (D-8 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (4 Gray) on D-1. Median age at time of UCBT was 14 (4-52) years. The median total nucleated cell number and CD34-positive cell number at infusion were 3.5 (1.07-7.87)× 107/kg and 1.7 (0.69-5.27) × 105/kg, respectively. Ciclosporin (CsA) and mycophenolate mofetil (MMF) was given to both groups as prophylaxis for graft versus host disease (GVHD).Results:Neutrophil recovery (>0.5×109/L) was observed in 11 patients of the ATG group and the median time to engraftment was 19 (13-35) days. The median time to platelet recovery (>20 × 109/L) was 40 (24-153) days. Primary graft failure was observed in seven patients. Only 1 out of 17 patients in the No-ATG group had primary graft failure. The median time to neutrophil engraftment was 17 (13-36) days. The median time to platelet engraftment was 31 (17-65) days. During follow-up, 7 patients died before 1 year due to non-engraftment (n=4), infection (n=2) and encephalorrhagia (n=1) in the ATG group. Four patients died in the No-ATG group due to infection (n=3) and IV grade acute GVHD in the skin and the intestinal tract (n=1, induced by discontinuing medicine). Furthermore, conditioning regimen without ATG shows even more superiority in patients refractory to immunosuppressive therapy with ATG and/or CsA (n=8), who had neutrophil engraftment completely within 20 days after cord blood infusion.Conclusion:UCBT after a FLU-CY-TBI conditioning regimen without ATG for SAA patients is better than that with ATG, especially for patients refractory to immunosuppressive therapy. Pediatric and adult SAA patients who are younger than 50 years old, lack of HLA-matched sibling donor and refractory to immunosuppressive therapy should consider UCBT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Improved Outcome of Unrelated Cord Blood Transplantation in Children with Severe Aplastic Anemia

IntroductionHematopoietic stem cell transplantation (HSCT) from an HLA-matched related donor is a first-line treatment for children with severe aplastic anemia (SAA). HSCT from an HLA-matched unrelated donor (MUD) is indicated as a salvage treatment for non-responders to immunosuppressive therapy (IST).Because unrelated cord blood transplantation (UCBT) has been considered as an experimental therapy, information of UCBT in patients with SAA is scarce, especially in pediatric patients. We analyzed the outcomes of UCBT in children with AA registered in the Transplant Registry Unified Management Program (TRUMP) conducted by the Japanese Society for Hematopoietic Cell Transplantation.Patients and MethodsBetween 1998 and 2013, 27 patients <15 years old who underwent an UCBT as the first HSCT were registered in the TRUMP database. Patients with congenital bone marrow failure syndrome such as Fanconi anemia were excluded from the analysis. Treatment failure were defined as death by all causes, graft failure (GF) and secondary malignancy. Data collected as October 2014 were analyzed.ResultsPatients' characteristicsAmong the 27 patients, 10 patients underwent UCBT during 1998 - 2005 and 17 patients underwent UCBT during 2006 - 2013. The median age at the time of UCBT was 6 years (range, 0 - 14). The male/female ratio was 12/15. The median interval between the diagnosis of AA and CBT was 212 days (range, 39 - 2,982). Sixteen patients received antithymocyte globulin (ATG) as immunosuppressive therapy (IST) before UCBT. The median total nucleated cell number and CD34 positive cell number at cryopreservation were 3.99 x 107/kg (range, 0.09 - 16.11 x 107/kg) and 1.31 x 105/kg (range, 0.39 - 6.17 x 105/kg), respectively. Ten patients received fludarabine (FLU) + cyclophosphamide (CY) + irradiation ± ATG. Six received FLU + CY + ATG. Four received FLU + melphalan (MEL) + irradiation and the remaining 7 received other various conditioning regimens. Cyclosporine was used in 9 patients and tacrolimus was used in 17 patients for graft-versus-host disease (GVHD) prophylaxis.Transplantation outcomesNeutrophil recovery was observed in 19 patients and the median time to engraftment was 20 days. Platelets engraftment was observed in 17 patients and the median time to engraftment was 50 days. One patient experienced secondary GF. Sustained engraftment was observed in 18 patients. Grade II - IV acute GVHD, limited chronic GVHD, and extensive chronic GVHD were observed in 6 (26%), 2 (10%), and 2 patients (10%), respectively.With median follow-up times of 18 months after CBT, 19 of 27 patients were alive. Causes of death included bacterial/fungus infections in 3, veno-occulusive disease (VOD) in 2, EBV-LPD, hematologic malignancy, and secondary GF in each 1 patient.The 5-year overall and failure-free survival (OS, FFS) of all patients were 69.5±9.0% and 59.3±9.5%, respectively. The 5-year OS and FFS of 17 patients who underwent UCBT after 2006 was 93.8±6.1% and 76.0±10.5%, respectively. Primary GF was observed in 8 patients, including 3 who underwent UCBT during 2006 - 2013. Two patients, who underwent UCBT after 2006, received FLU + CY + ATG without irradiation and remaining one patient received CY + ATG + total body irradiation (TBI). We screened anti-HLA antibodies in 8 patients but none of them were positive. The conditioning regimens including ATG exhibited a significantly worse FFS than those without ATG (33.3±12.2 % vs 91.7±8.0 %, P=0.004). On the other hand, the conditioning regimens including irradiation exhibited a better FFS than those without irradiation (75.0±9.7 % vs 14.3±13.2 % , P=0.01). The 5 year FFS of FLU + MEL + irradiation regimen (n=4) and FLU + CY + irradiation regimen (n=10) was 100% and 90%±9.5%, respectively.Univariate analysis resulted in no statistical significant differences in OS and FFS in HLA disparities, total nucleated cell number and CD34 positive cell number at cryopreservation, and methods of GVHD prophylaxis. One patient developed secondary malignancy.DiscussionOur study showed that a reduced conditioning regimen with Flu, MEL/CY and low-dose irradiation may be an optimal regimen for SAA children receiving UCBT. An important finding is that ATG has no benefit in this setting. A prospective study with larger number of patients is warranted to confirm our promising results. DisclosuresKojima:SANOFI: Honoraria, Research Funding.

Impact of HLA of Winning Cord Blood Unit on Outcomes after Double Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee Cellular Therapy and Immunobiology Working Party and the Acute Leukemia Working Party of the EBMT

Umbilical cord blood transplantation (UCBT) from unrelated donor is a valid alternative for patients (pts) with acute leukemia (AL) who lack an HLA matched donor. Double UCBT (dUCBT) has extended the use of UCBT to adults. In the majority of the cases, chimerism analysis shows that one unit emerges as the sole source of long term hematopoiesis in the recipient (rcp) following dUCBT. However, no clear factor has yet been identified to reliably predict which unit will emerge as the predominant one.With the aim of analyzing factors that may predict cord blood unit (CBU) predominance and the impact of the winning CBU characteristics on outcomes after dUCBT, we studied adults with AL who underwent dUCBT as first transplant between 2004 and 2013 at EBMT centres. We selected pts who achieved engraftment and who had available chimerism data assessed within day 130 after dUCBT, with one of the CBUs representing at least 50% of the rcp hematopoiesis (winCBU). According to these criteria, 347 pts were included: 323 had full donor (18 being dual chimera) and 24 had mixed chimerism (>5% of donor cells). At diagnosis, 35% had ALL and 65% AML. At dUCBT 45% were in first complete remission (CR), 44% in second CR and 11% had more advanced disease. Overall, 33% had high risk cytogenetic features. Median time from diagnosis to dUCBT was 12 months (range, 2-202), median age was 40 years (y) (18-76). Conditioning regimen (CT) was reduced intensity (RIC) in 52%. Cyclophosphamide+fludarabine+total body irradiation was the most frequent CT (63%). Anti-thymoglobulin (ATG) was administrated in 25% of the transplants. Median number of total nucleated cells (TNC) and CD34+ cells at cryopreservation were 5.1x107/Kg (range, 2.3-13.7) and 1.3x105/Kg (range, 0.4-10.7), respectively. Considering the unit with the highest number of HLA mismatches (MMs) with the rcp, 73% of the donors were matched at 4 or less loci (≤4/6). For winCBUs, median number of TNC and CD34 cells at cryopreservation were 2.5x107/Kg (range, 0.95-6) and 1x105/Kg (range, 0.06-10), respectively. Only 4% of the winCBUs were 6/6 HLA-matched to the rcp, while 37% were 5/6, 55% were 4/6 and 4% were 3/6 HLA-matched. Overall, 54% of the winCBUs were gender matched and 38% were ABO compatible with the rcp. WinCBUs median age was 3.4 years (range, 0.2-14). As for inter unit characteristics, 50% of the pts received gender matched units. Units were ABO compatible in 40% of the cases, while 30% had minor and 30% had major ABO incompatibility.In our study population, median follow-up for survivors was 35 months (range, 3-99). All pts engrafted with neutrophil >0.5x109/L in a median time of 25 days (range, 6-66) post DCBT. No secondary graft failure was reported. The cumulative incidence (CI) of acute GvHD grade II-IV at 100 days was 41% with a median time of onset of 29 days (range, 7-106). The 3y-CI of chronic GvHD was 41% (50% of the pts had extensive). The 3y-CI of relapse (RI) and transplant related mortality (TRM) were 27% and 24%, respectively. At 3y, leukemia free survival (LFS) was 49% and overall survival (OS) was 54%.In multivariate analysis (MVA) including unit characteristics (HLA and gender matching, type of HLA MMs, number of TNC and CD34 cells at cryopreservation, ABO compatibility and unit age) and inter unit features (gender match, ABO compatibility), no significant factor predicting the winCBU was identified.Analyzing the impact of winCBU on dUCBT outcomes, the HLA matching between CBU and the rcp was the only characteristic related to the winCBU significantly affecting results. The 3y-LFS for pts with 6/6 or 5/6 HLA-matched winCBUs was 56% as compared to 44% for those with 4/6 (p=0.03), while OS was 62% versus 49% (p=0.01), respectively. Acute GvHD was increased in pts receiving a 4/6 HLA-matched winCBU (46% versus 35% for those 6/6 or 5/6, p=0.04). In MVA, 4/6 HLA-matched winCBU was associated with decreased LFS (HR 1.5, p=0.03) and OS (HR 1.5, p=0.03), and with increased TRM (HR 1.9, p=0.03) and acute GvHD (HR 1.7, p=0.01). Notably, older winCBUs (>3.4y) were associated with higher acute GvHD (48% versus 35%; HR 1.6, p=0.02). Other factors associated with poor outcomes were advanced disease status and the use of ATG.Although we failed to identified any factor predicting CBU predominance, we were able to demonstrate that a 4/6 HLA matched winCBU is associated with poor outcomes. Therefore, selecting units with lower number of HLA MMs for dUCBT may improve final outcomes. DisclosuresRussell:Therakos: Other: shares. Mohty:Riemser: Honoraria, Research Funding. Nagler:Biokine LTD: Consultancy.

Reduced-Intensity Unrelated Cord Blood Transplantation for Adult Patients with Severe Aplastic Anemia

Although unrelated cord blood transplantation (UCBT) has become a viable therapeutic option widely applicable for adult patients with hematological diseases, UCBT for severe aplastic anemia (SAA) remains to be controversial due to higher incidence of graft failure (GF) relative to the other stem cell sources. To evaluate the feasibility of UCBT for SAA, we retrospectively analyzed results for 11 adult patients with SAA who received first UCBT after reduced-intensity conditioning regimen (RI-UCBT) in Toranomon Hospital. Median age was 49 years (range, 20–70). Nine of them were non-responders to intensive immunosuppressive therapy and were multiply transfused, and two patients were fulminant type with no neutrophils in peripheral blood at diagnosis. The conditioning regimen consisted of fludarabine 125mg/m2, melphalan 80mg/m2, and 4 Gy of total body irradiation. Graft-versus-host disease prophylaxis was composed of cyclosporine alone (n=2), tacrolimus alone (n=2), and tacrolimus plus mycophenolate mofetil (n=7). Median total nucleated cell number and median CD34+ cell number were 2.65 × 107/kg (range, 1.83–4.39) and 0.70 × 105/kg (range, 0.27–1.52), respectively. Serological HLA disparities were as follows; 6/6 (n=3), 5/6 (n=2), and 4/6 (n=6). Ten of the 11 patients achieved primary neutrophil and platelet engraftment. Median time to an absolute neutrophil count > 0.5×109/liter and an unsupported platelet count > 20×109/liter were 18 days (range, 12–28) and 42.5 days (range, 26–64) respectively. All patients who achieved engraftment resulted in complete hematological recovery with complete donor chimerism, except for one patient who developed late GF at three years after UCBT. All 2 who experienced GF (1: primary GF, 1: late GF) were rescued by second RI-UCBT. Two of the 11 patients died from IPS (n=2), and remaining 9 patients are alive, having survived for 18.7 months (range, 2–71 months). Six out of 7 patients who survived more than 6 months were free from immunosuppressant. The probabilities of overall survival and event-free survival at 2 years after UCBT were 77.8% and 68.2%, respectively. Our results here strongly indicated feasibility and effectiveness of RI-UCBT for adult SAA patients with high engraftment rate and low treatment-related mortality. RI-UCBT could be considered as a viable therapeutic option for those who lack suitable HLA-matched sibling donors and failed immunosuppressive therapy.