In Japan only single cord blood transplantations (CBTs) are typically performed and their number has increased over 23 years, with ongoing improvement in the results. CBTs with multiple HLA mismatches are usually employed due to a low HLA barrier, and lower engraftment rate is one of problems to overcome. Here, as part of efforts to improve guidelines for the selection and processing of cord blood units for transplantation, we sought to assess the present status of CBTs in Japan, and to elucidate factors contributing to the favorable outcomes, especially focusing on the selection by cell components of cord blood (CB) unit and HLA allele matching. We conducted a nation-wide study analyzing 13,443 patients who underwent first CBT between in Japan between Dec 1997 - Dec 2019 using multivariate regression analysis. Both patient and transplant related variables, such as age and HCT-CI scores, as well as selectable CB unit characteristics were included in the analysis. The interaction analysis elucidated that CB unit selection favoring larger numbers of CD34⁺ cells /kg and CFU-GM number/kg, and not total nucleated cell number/kg contributed to improved engraftment after transplantation. Moreover, a higher CD34+ cell dose was associated with improved overall survival. Distinctive HLA allele matching was observed. 0-1 HLA allele mismatch between patient and donor had favorable engraftment and carried a significantly lower risk of acute GVHD and chronic GVHD, but had a significantly higher leukemia relapse rate, compared with a 3-HLA allele mismatch. HLA-DRB1 mismatches were associated with reduced risk of leukemia relapse. Notably, the number of HLA allele mismatches had no incremental effect on engraftment, acute and chronic GVHD, or relapse incidence. As a result, the 5-year overall survival did not differ significantly between patients receiving CB units with 0-7 HLA allele mismatches. Main points of CB unit selection: First, selection according to a higher number of CD34+/kg and then of CFU-GM/kg is recommended to obtain favorable engraftment. A unit with 0.5 x 10⁵ CD34+/kg is minimally acceptable. For units with a CD34⁺ cell dose of 0.5-1.0 x 10⁵ cells/kg, applying the parameter of ≥20 - 50 x 10³ CFU-GM/kg (66.5% of transplanted CB units in this cohort) is associated with a neutrophil engraftment rate of approximately 90%. A unit with ≥1.0 x 10⁵ CD34⁺/kg can achieve a ≥90% mean neutrophil engraftment rate. Subsequently, HLA allele matching of HLA-A, -B, -C, -DRB1 at the 2-field level should be searched for unit with 0-1 HLA allele mismatch number in HVG direction for favorable engraftment. Unit with 2-6 HLA allele mismatches is acceptable in adult patients (15 y.-) and unit with 2-4 HLA allele mismatches in pediatric patients (0-14 y.). Unit with HLA-DRB1 and/or -B allele mismatch might not be preferable due to an increased GVHD risk. Our analysis demonstrated that single CBT with the selection of adequate CD34⁺/kg and CFU-GM/kg, and HLA allele matching showed a favorable outcome not only in pediatric but also in adult patients.

Aplastic anemia patients who are refractory to immunosuppressive therapy or with very low neutrophil counts require allogeneic hematopoietic stem cell transplantation (HSCT). Umbilical cord blood transplantation (UCBT) has been a treatment option when an HLA-matched donor is not available, and HSCT from a related haploidentical donor using post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis (PTCy-haplo) recently became another important approach. We aimed to compare the outcomes of PTCy-haplo and UCBT in adult patients with aplastic anemia to identify more effective and safer approaches for alternative donor transplantation. Data in a nationwide registry were analyzed retrospectively to assess the outcomes of aplastic anemia patients age ≥16 years who underwent PTCy-haplo or UCBT as their first HSCT between 2016 and 2020. The primary endpoint was 1-year overall survival (OS) after HSCT. Secondary endpoints included 1-year failure-free survival (FFS), neutrophil and platelet engraftment, and acute and chronic GVHD. Eighty-three patients who underwent PTCy-haplo (n = 24) or UCBT (n = 59) were eligible. The 1-year OS rate was 78.5% (95% confidence interval [CI], 55.7% to 90.5%) in the PTCy-haplo group and 77.5% (95% CI, 64.5% to 86.3%; P = .895) in the UCBT group. The 1-year FFS rate was 78.7% (95% CI, 56.1% to 90.6%) in the PTCy-haplo group and 62.2% (95% CI, 48.5% to 73.3%; P = .212) in the UCBT group. Among patients age <40 years, the PTCy-haplo group had a significantly higher FFS rate (92.9% [95% CI, 59.1% to 99.0%]) vs 63.9% [95% CI, 43.2% to 78.7%]; P = .047). Neutrophil engraftment and platelet engraftment rates were significantly higher in the PTCy-haplo group compared with the UCBT group: 95.8% (95% CI, 73.9% to 99.4%) vs 78.0% (95% CI, 65.1% to 86.6%, P < .001) and 83.3% (95% CI, 61.5% to 93.4%) vs 72.9% (95% CI, 59.6% to 82.4%; P = .025). No significant difference was observed in the cumulative incidence of grade II-IV acute GVHD and chronic GVHD between the 2 groups. Aplastic anemia patients achieved significantly higher neutrophil and platelet engraftment rates with PTCy-haplo than with UCBT. OS and the incidences of acute and chronic GVHD were similar between the 2 groups. In patients age <40 years, the FFS rate was higher in the PTCy-haplo group. PTCy-haplo is promising for alternative donor transplantation in adult patients with aplastic anemia.

The effect of single or multiple mismatches at each HLA locus on outcomes after cord blood transplantation (CBT) is controversial. We analyzed the effects of single or multiple HLA locus mismatches on the outcomes after single CBT using Japanese registry data from the Japan Society for Hematopoietic Cell Transplantation. Patients age ≥16 years with acute leukemia and myelodysplastic syndromes who underwent their first CBT between 2003 and 2017 (n = 4074) were included. The effect of the number of HLA locus mismatches (0, 1, or 2 for the HLA-A, -B, -C, and -DRB1 loci) on outcomes was analyzed after adjusting for other significant variables. The patient cohort had a median age of 54 years. The median total nucleated and CD34 cell doses were 2.6 × 10⁷/kg and .8 × 10⁵/kg, respectively. The number of CBTs with single or double mismatches were 2099 and 292, respectively, for the HLA-A locus, 2699 and 341 for the HLA-B locus, 2555 and 609 for the HLA-C locus, and 2593 and 571 for the HLA-DRB1 locus. Single and double HLA-DRB1 mismatches were associated with a higher risk of grade II-IV acute graft-versus-host disease (GVHD; single: hazard ratio [HR], 1.29, P < .001; double: HR, 1.49, P < .001; P for trend <.001). Single and double mismatches at HLA-DRB1 as well as single mismatches at HLA-A and HLA-B also were associated with grade III-IV acute GVHD. Single and double HLA-B mismatches and double HLA-DRB1 mismatches were associated with a high risk of nonrelapse mortality (NRM). On the other hand, double mismatches at HLA-A or HLA-DRB1 and single mismatches at HLA-B were associated with a lower risk of relapse. HLA-DRB1 double mismatch was associated with high risk of grade II-IV and grade III-IV acute GVHD and NRM but lower risk of relapse. Not only the locus mismatch, but also the number of mismatches, should be considered in cord blood unit selection.

Thin-film S/N heterostructures of superconducting BiSrCaCuO and metallic BiSrCuO with good surface morphology, crystallinity, and superconducting properties were formed on (100) MgO substrates by halide chemical vapor deposition (CVD). Critical temperatures (T _c at zero resistance) and critical current densities (J _c) of the BiSrCaCuO films on MgO substrate were T _c=75 to 80 K and J _c=1×10⁶ A/cm² at 60 K. Resistivity of the metallic BiSrCuO films was 0.7 to 1.5×10^-3 Ω·cm from 10 to 300 K. High-resolution transmission electron microscopy (HRTEM) images showed the interface between the BiSrCaCuO and BiSrCuO films to be atomically abrupt. The critical temperature of S/N multilayer samples was about 75 K.