Search

Summary: The impact of human leukocyte antigen (HLA) mismatching at the HLA‐A, ‐B, ‐C, and ‐DRB1 loci after unrelated bone marrow transplantation in paediatric patients with haematological malignancies has not been fully examined. Here, we analysed patients with haematological malignancies (all aged ≤15 years; n = 1330) who underwent a first unrelated bone marrow transplantation between 1993 and 2017 in Japan. The results show that although an HLA mismatch was significantly associated with a low relapse rate, it was also associated with higher non‐relapse mortality. There was a significant association between HLA mismatch and low overall survival. Locus mismatch analysis revealed that, as in adults, an HLA‐C mismatch had a significant negative impact on survival; however, in paediatric patients, an HLA‐DRB1 mismatch did not have a negative impact, although these HLA mismatch effects are weakened in recent cases. Taken together, the results suggest that an HLA‐matched donor should be the first candidate for paediatric patients; however, for patients without a matched sibling or matched unrelated donor, we can select an unrelated donor with a mismatch at HLA‐DRB1 if available. [ABSTRACT FROM AUTHOR]

Background: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time and outcomes in accidental hypothermia (AH) patients compared to those of patients without AH has not been fully investigated. Methods: This was a secondary analysis of the retrospective multicenter registry in Japan. We enrolled patients aged ≥ 18 years who had been admitted to the emergency department for OHCA and had undergone ECPR between January, 2013 and December, 2018. AH was defined as an arrival body temperature below 32 °C. The primary outcome was survival to discharge. Cubic spline analyses were performed to assess the non-linear associations between low-flow time and outcomes stratified by the presence of AH. We also analyzed the interaction between low-flow time and the presence of AH. Results: Of 1252 eligible patients, 105 (8.4%) and 1147 (91.6%) were in the AH and non-AH groups, respectively. Median low-flow time was 60 (47–79) min in the AH group and 51 (42–62) min in the non-AH group. The survival discharge rates in the AH and non-AH groups were 44.8% and 25.4%, respectively. The cubic spline analyses showed that survival discharge rate remained constant regardless of low-flow time in the AH group. Conversely, a decreasing trend was identified in the survival discharge rate with longer low-flow time in the non-AH group. The interaction analysis revealed a significant interaction between low-flow time and AH in survival discharge rate (p for interaction = 0.048). Conclusions: OHCA patients with arrival body temperature < 32 °C who had received ECPR had relatively good survival outcomes regardless of low-flow time, in contrast to those of patients without AH. [ABSTRACT FROM AUTHOR]

Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11–20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R000041577 (unique identifier: UMIN000036490). [ABSTRACT FROM AUTHOR]

Background: Adrenoleukodystrophy (ALD) is an X‐linked recessive disorder and 30–40% of patients develop progressive cerebral neurodegeneration. For symptomatic ALD patients, allogeneic stem cell transplantation (SCT) is considered the standard treatment modality to stabilize or prevent the progression of neurological symptoms. Methods: We retrospectively analyzed the transplant outcomes of 99 pediatric patients with cerebral ALD in Japan. The conditioning regimens included Regimen A: fludarabine/melphalan/low‐dose total body irradiation (TBI) with brain sparing (n = 39), Regimen B; busulfan/cyclophosphamide ± others (n = 23), Regimen C: melphalan/total lymphoid irradiation/thoracoabdominal irradiation ± anti‐T lymphocyte globulin ± fludarabine (n = 27), and Regimen D: others (n = 10). Results: The 5‐year overall survival (OS) and event‐free survival (EFS) of all patients were 90.0% and 72.9%, respectively. The 5‐year OS was 100.0% for Regimen A, 91.1% for Regimen B, 84.4% for Regimen C, and 67.5% for Regimen D (p = 0.028). The 5‐year EFS was 78.3% for Regimen A, 78.0% for Regimen B, 70.4% for Regimen C, and 48.0% for Regimen D (p = 0.304). The OS marginally improved after 2007 compared with before 2006 (95.3% vs. 85.2%, p = 0.066), due to the improvement of cord blood transplantation (CBT) outcomes after 2007 compared with before 2006 (96.6% vs. 68.4%, p = 0.005). On magnetic resonance imaging of the brain, a reduced Loes score after SCT was only observed in one of the 15 bone marrow transplantation (BMT) patients, but in 5 of the 15 CBT patients (p = 0.173). Conclusions: Our study revealed that a reduced conditioning regimen with fludarabine/melphalan/low‐dose TBI provides better outcomes, and the results of CBT significantly improved after 2007. [ABSTRACT FROM AUTHOR]

The combined effects of HLA-allele matching at six-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and CD34+ cell dose on clinical outcomes were analyzed in 1,226 adult cases with single-unit unrelated cord blood transplantation. In the six-loci analysis, low HLA-allele matches did not significantly increase the overall mortality compared to higher matches, whereas in the five-loci analysis excluding HLA-DPB1, they caused a higher overall mortality (HR 1.42, p =.002), possibly due to the graft-versus-leukemia effect of HLA-DPB1 mismatches. A lower CD34+ cell dose (<.50 × 105/kg) resulted in higher mortality and lower engraftment; these inferior outcomes were offset by high HLA-allele matches (7-10/10 match), while the inferior outcomes of low HLA-allele matches were improved by increasing the CD34+ cell dose. Consideration of the combined effects of the CD34+ cell dose and HLA matching may expand the options for transplantable units when HLA matching or the CD34+ cell dose is inadequate. [ABSTRACT FROM AUTHOR]