Allogeneic stem cell transplantation for inherited metabolic disorders: 35 years' experience at a single institution.

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning.

Point-of-Care Ultrasound (POCUS)-Guided Management of Cardiogenic Shock in COVID-19 Fulminant Myocarditis With Combined Veno-Arterial Extracorporeal Membrane Oxygenation and Impella (ECPELLA): A Case Report.

The COVID-19 pandemic, which has been raging globally, has been reported to cause not only pneumonia but also various cardiovascular diseases. In particular, myocarditis poses a serious risk if it becomes severe. As a characteristic of myocardial damage in this disease, right ventricular dysfunction is frequently reported, and biventricular failure is not uncommon. In cases where cardiogenic shock occurs, ECPELLA, which combines veno-arterial extracorporeal membrane oxygenation and Impella, is used for management. Currently, in Japan, ECPELLA is the central treatment for severe biventricular failure in the acute phase. However, its management method has not been established. Weaning from ECPELLA requires the following three conditions: (1) improvement of left ventricular function; (2) improvement of right ventricular function; and (3) optimization of circulating plasma volume. However, since these conditions change moment by moment, frequent and detailed assessments are necessary. Nevertheless, considering the need for isolation due to COVID-19, there are limitations on the tests that can be performed. In this regard, point-of-care ultrasound (POCUS) allows repeated bedside evaluations while maintaining infection protection. We report that in the case of severe COVID-19-related myocarditis, the use of POCUS enabled the preservation of cardiac function and appropriate timing for weaning from ECPELLA.

Synthesis of nucleoside oligophosphates by electrophilic activation of phosphorothioate.

We herein report a new synthetic method for nucleoside oligophosphates based on electrophilic activation of 5'-phosphorothioate nucleotides. The treatment of phosphorothioate with 2,4-dinitrochlorobenzene (DNCB) efficiently afforded the key activated species, electrophilic thioester nucleotides (EPT-Ns), which were coupled with various phosphate reagents to afford the target nucleoside oligophosphates, including an mRNA cap analog.

Impact of human leukocyte antigen mismatch on outcomes after unrelated bone marrow transplantation in paediatric patients: A retrospective analysis by the JSTCT HLA working group.

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.

Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan.

BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

The impact of lesion complexity on predicting mortality of coronary artery disease patients after out-of-hospital cardiac arrest.

INTRODUCTION: Coronary artery disease (CAD) is the most frequent cause of out-of-hospital cardiac arrest (OHCA). Nevertheless, there have been limited studies focusing on the impact of lesion complexity on resuscitated CAD patients. The purpose of the present study was to investigate the association between coronary lesion complexity and the mortality of CAD patients after OHCA. METHODS: From pooled database of two centers, which comprised 706 successfully resuscitated OHCA patients, 172 patients undergoing coronary angiography were retrospectively investigated. A total of 148 patients exhibited coronary stenosis on angiogram and were included in the final analysis. Baseline characteristics, pre-and post-hospital care, general status after resuscitation and angiographical findings were compared between the patients who deceased within 30 days and those who survived and the predictors of 30-day mortality were determined. RESULTS: Ninety-four patients (63.5%) survived at 30 days. Bystander cardiopulmonary resuscitation (CPR) (Odds ratio (OR) 0.36; 95% confidence interval (CI) 0.14-0.96; P = 0.041), revascularization of coronary stenosis (OR 0.15; 95% CI 0.19-0.86; P < 0.001), GRACE risk score (OR 1.04; 95% CI 1.02-1.05; P < 0.001) and SYNTAX score (OR 1.07; 95% CI 1.01-1.13; P = 0.025) were independent predictors of 30-day mortality. As multiple predictors such as bystander CPR, GRACE score and SYNTAX score were combined, the 30-day mortality gradually deteriorated. CONCLUSIONS: In addition to bystander CPR, GRACE score and revascularization, SYNTAX score independently predicted 30-day mortality of CAD patients after OHCA.

Stem cell transplantation for pediatric patients with adrenoleukodystrophy: A nationwide retrospective analysis in Japan.

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.

Combined impact of HLA-allele matching and the CD34-positive cell dose on optimal unit selection for single-unit cord blood transplantation in adults.

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.

Impact of the combination of donor age and HLA disparity on the outcomes of unrelated bone marrow transplantation.

Impact of donor age considering HLA disparity on hematopoietic cell transplantation (HCT) outcomes has not been fully evaluated. We evaluated 8486 patients who received unrelated bone marrow transplantation (UR-BMT) from 8/8 or 7/8 HLA-matched donors. Compared to 8/8 HLA-matched younger donors (<40 years), 8/8 HLA-matched older donors (subdistribution hazard ratio [SHR], 1.16; 95% CI, 0.97-1.38) and 7/8 HLA-matched younger donors (SHR, 1.33; 95% CI, 1.11-1.58) were associated with increased risk of grade III-IV acute graft-versus-host disease (aGVHD). 7/8 HLA-matched older donors had further increased risk (SHR, 2.00; 95% CI, 1.68-2.38) due to interaction between donor age and HLA disparity (p for interaction = 0.038). Progression-free survival (PFS) after UR-BMT with 8/8 HLA-matched younger donors was comparable to that after UR-BMT with 8/8 HLA-matched older donors, whereas UR-BMT with 7/8 HLA-matched younger or older donors was significantly associated with lower PFS than UR-BMT with 8/8 HLA-matched younger donors (younger donor; HR, 1.12; 95% CI, 1.04-1.21, older donor; HR, 1.28; 95% CI, 1.17-1.40; p for interaction = 0.079). In conclusion, adverse effect of increased donor age requires attention, especially in HLA-mismatched UR-BMT due to interaction between donor age and HLA disparity. Intensive aGVHD prophylaxis may be required to improve outcomes after HCT with mismatched older donors.

Catheter ablation for atrial fibrillation in patients with congestive heart failure.

BACKGROUND: We evaluated the 1-year success rate of maintaining sinus rhythm after catheter ablation (CA) for atrial fibrillation (AF) in patients with or without congestive heart failure (CHF). METHODS: In this single-centre retrospective matched-pair cohort study of 3,018 AF patients who underwent initial CA between January 2012 and June 2018, 227 pairs with (CHF group) or without CHF (control group) were matched using propensity scores. In the CHF group, 108 patients were assigned to the arrhythmia-induced cardiomyopathy (AIC) group whose left ventricular systolic dysfunction was explained only by lasting AF or atrial tachycardia; the remaining 119 had organic heart diseases (non-AIC group). We evaluated the 1-year AF-free survival and changes in clinical findings before and after CA. RESULTS: The CHF and control groups showed similar AF-free survival; however, AIC patients had significantly better survival than non-AIC patients. AF recurrence was significantly related to CHF re-hospitalisation, which was significantly more frequent in the non-AIC group than in the AIC group. The clinical outcomes of left atrial dilation, brain natriuretic peptide level, and left ventricular ejection function improved significantly before and after CA in both groups. The degree of improvement was significantly better in the AIC group than in the non-AIC group. CONCLUSIONS: The 1-year success rate was not significantly different between the CHF and control groups. The 1-year success rate in the AIC group was similar to that in the AIC-control group and was better than that in the non-AIC group. CHF clinical outcomes were improved significantly.

Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method.

The highly polymorphic human major histocompatibility complex (MHC) also known as the human leukocyte antigen (HLA) encodes class I and II genes that are the cornerstone of the adaptive immune system. Their unique diversity (>25,000 alleles) might affect the outcome of any transplant, infection, and susceptibility to autoimmune diseases. The recent rapid development of new next-generation sequencing (NGS) methods provides the opportunity to study the influence/correlation of this high level of HLA diversity on allele expression levels in health and disease. Here, we describe the NGS capture RNA-Seq method that we developed for genotyping all 12 classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DRB5) and assessing their allelic imbalance by quantifying their allele RNA levels. This is a target enrichment method where total RNA is converted to a sequencing-ready complementary DNA (cDNA) library and hybridized to a complex pool of RNA-specific HLA biotinylated oligonucleotide capture probes, prior to NGS. This method was applied to 161 peripheral blood mononuclear cells and 48 umbilical cord blood cells of healthy donors. The differential allelic expression of 10 HLA loci (except for HLA-DRA and HLA-DPA1) showed strong significant differences (P < 2.1 × 10-15). The results were corroborated by independent methods. This newly developed NGS method could be applied to a wide range of biological and medical questions including graft rejections and HLA-related diseases.

The Sequential Organ Failure Assessment (SOFA) score predicts mortality and neurological outcome in patients with post-cardiac arrest syndrome.

BACKGROUND: Patients experiencing out-of-hospital cardiac arrest (OHCA) and subsequent post-cardiac arrest syndrome are often compromised by multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score has been used to predict clinical outcome of patients requiring intensive care for multi-organ failure. Thus, the assessment of SOFA score is recommended as a criterion for sepsis. Although post-cardiac arrest patients frequently develop sepsis-like status in ICU, there are limited reports evaluating the SOFA score in post-cardiac arrest patients. We investigated the predictive value of the SOFA score in survival and neurological outcomes in patients with post-cardiac arrest syndrome. METHODS: A total of 231 cardiovascular arrest patients achieving return of spontaneous circulation (ROSC) were finally extracted from the institutional consecutive database comprised of 1218 OHCA patients transferred to the institution between January 2015 and July 2018. The SOFA score was calculated on admission and after 48h. Predictors of survival and neurological outcome defined as having cerebral-performance-category (CPC) 1 or 2 at 30 days were determined. RESULTS: SOFA score was lower in survived patients (5.0 vs 10.0, p<0.001) and those with favorable neurological outcome (5.0 vs 8.0, p<0.001) as compared with the counterparts. The SOFA score on admission was an independent predictor of survival (OR 0.68, 95% confidence interval [CI] 0.59-0.78; p<0.001) and favorable neurological performance (OR 0.79; 95% CI 0.69-0.90; p<0.001) at 30 days. Furthermore, a change in SOFA score (48-0h) was predictive of favorable 30-day neurological outcome (OR 0.71, 95% CI 0.60-0.85; p<0.001). CONCLUSIONS: Evaluation of the SOFA score in the ICU is useful to predict survival and neurological outcome in post-cardiac arrest patients.

Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings.

Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs.

Long-term outcome and chimerism in patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation: a retrospective nationwide survey.

We analyzed the outcomes of allogeneic stem cell transplantation (SCT) and risk factors for chimerism in 108 patients with Wiskott-Aldrich syndrome (WAS) who were registered with The Japan Society for Hematopoietic Cell Transplantation between January 1985 and December 2016. A preparative conditioning regimen consisting of myeloablative conditioning (MAC) was provided to 76 patients, and reduced-intensity conditioning was provided to 30 patients. Fifty-one patients received prophylaxis against graft-versus-host disease (GVHD) with cyclosporine, and 51 patients received tacrolimus (Tac). Chimerism analyses had been performed in 91 patients. Neutrophil engraftment was achieved in 91 patients (84.3%). The engraftment rate was significantly higher in patients who received Tac for GVHD prophylaxis (p = 0.028). Overall survival rate (OS) was significantly higher in patients with complete chimerism than in patients with mixed chimerism (88.2 ± 6.1% and 66.7 ± 9.9%, respectively, p = 0.003). Multivariate analysis showed that the rate of complete chimerism in patients who received MAC including cyclophosphamide (CY) at a dose of 200 mg/kg was significantly higher (p = 0.021) than that in patients who received other conditioning. Thus, MAC including CY at a dose of 200 mg/kg and Tac for GVHD prophylaxis were optimal conditions of SCT for patients with WAS under existing study.

Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice.

The immune system encompasses acquired and innate immunity that matures through interaction with microenvironmental components. Cytokines serve as environmental factors that foster functional maturation of immune cells. Although NOD/SCID/IL2rgKO (NSG) humanized mice support investigation of human immunity in vivo, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune function. To study the roles of human cytokines in human acquired and innate immune cell development, we created NSG mice expressing hIL-7 and hIL-15. Although hIL-7 alone was not sufficient for supporting human NK cell development in vivo, increased frequencies of human NK cells were confirmed in multiple organs of hIL-7 and hIL-15 double knockin (hIL-7xhIL-15 KI) NSG mice engrafted with human hematopoietic stem cells. hIL-7xhIL-15 KI NSG humanized mice provide a valuable in vivo model to investigate development and function of human NK cells.

Co-activation of macrophages and T cells contribute to chronic GVHD in human IL-6 transgenic humanised mouse model.

BACKGROUND: Graft-versus host disease (GVHD) is a complication of stem cell transplantation associated with significant morbidity and mortality. Non-specific immune-suppression, the mainstay of treatment, may result in immune-surveillance dysfunction and disease recurrence. METHODS: We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34+CD38-CD45RA- haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34- cells mimicking acute GVHD. We characterised human immune cell subsets, target organ infiltration, T-cell repertoire (TCR) and transcriptome in the humanised mice. FINDINGS: In cGVHD humanised mice, we found activation of T cells in the spleen, lung, liver, and skin, activation of macrophages in lung and liver, and loss of appendages in skin, obstruction of bronchioles in lung and portal fibrosis in liver recapitulating cGVHD. Acute GVHD humanised mice showed activation of T cells with skewed TCR repertoire without significant macrophage activation. INTERPRETATION: Using humanised mouse models, we demonstrated distinct immune mechanisms contributing acute and chronic GVHD. In cGVHD model, co-activation of human HSPC-derived macrophages and T cells educated in the recipient thymus contributed to delayed onset, multi-organ disease. In acute GVHD model, mature human T cells contained in the graft resulted in rapid disease progression. These humanised mouse models may facilitate future development of new molecular medicine targeting GVHD.

Comparison of HLA Allele Mismatch and Antigen Mismatch in Unrelated Bone Marrow Transplantation in Patients with Leukemia.

We compared the effect of HLA single-antigen and single-allele mismatched unrelated bone marrow transplantation (UBMT) without in vivo/ex vivo T cell depletion. Becasue a single DRB1 mismatch is preferred among 1-allele or 1-antigen mismatched donors, we performed mismatched allele- or antigen-specific analyses with a single DRB1 mismatch as the reference. In adjusted comparison by multivariate analyses, an HLA-DRB1 single-allele mismatch resulted in a decreased risk of nonrelapse mortality (NRM; relative risk [RR], 1.33; 95% confidence interval [CI], 1.08 to 1.63, P = .006) compared with an HLA-DR single-antigen mismatch and conferred a decreased risk of NRM (RR, 1.25; 95% CI, 1.01 to 1.57; P = .025) and overall mortality (RR, 1.16; 95% CI, 1.00 to 1.37; P = .046) compared with an HLA-C single-antigen mismatch. Relative to an HLA-DRB1 single-allele mismatch, 2-mismatch transplants, including those with 1 or more antigen mismatches, resulted in a significantly increased risk of NRM (1-antigen/1-allele mismatch: RR, 1.68; 95% CI, 1.03 to 2.05; P < .001; 2-antigen mismatch: RR, 1.58; 95% CI, 1.04 to 2.02; P = .001) and overall mortality (1-antigen/1-allele mismatch: RR, 1.27; 95% CI, 1.09 to 1.47; P = .002; 2-antigen mismatch: RR, 1.27; 95% CI, 1.03 to 1.57; P = .02). NRM correlated with the combined number of mismatches and allele or antigen mismatches, with rates of 22%, 27%, 32%, 31%, and 38% at 4years for full match, single-allele mismatch, single-antigen mismatch, 2-allele mismatch, and 2 mismatches that included an antigen mismatch, respectively. Our results support the preference for an allele mismatch rather than an antigen mismatch in unrelated bone marrow donors with 1 DR mismatch or 2 mismatches for T cell-replete UBMT.

Effects of HLA mismatch on cytomegalovirus reactivation in cord blood transplantation.

Although human leukocyte antigen (HLA) mismatch is often thought to be associated with a high incidence of cytomegalovirus (CMV) reactivation, it is not clear whether this process is mediated by HLA mismatch or other factors, such as acute graft-versus-host disease (aGVHD). Here we focused on cord blood transplantation (CBT) and examined the effects of HLA mismatch on the incidence of CMV reactivation while minimizing the effects of aGVHD. In a multivariate analysis considering aGVHD as a time-dependent covariate, a significant effect on the incidence of CMV reactivation was noted for HLA disparity (hazard ratio [HR]: 0.54 for 8/8 match compared with 3-allele mismatch) and development of aGVHD (HR: 1.26). Next, in an analysis excluding cases that developed aGVHD, the incidences of CMV reactivation for 8/8 match and 1-allele mismatch were low compared with those for other mismatches. These findings were supported by the multivariate analysis (HR: 0.49 for 8/8 match and 0.64 for 1-allele mismatch compared with 3-allele mismatch). Together, these results suggested that HLA mismatch was involved in CMV reactivation and was associated with high morbidity of opportunistic infection after CBT.

Propensity-matched comparison of cryoballoon and radiofrequency ablation for atrial fibrillation in elderly patients.

BACKGROUND: Pulmonary vein isolation (PVI) with a cryoballoon (CB) is an effective treatment for atrial fibrillation (AF). The efficacy of CB PVI for elderly patients with AF remains unclear. OBJECTIVE: We aimed to analyze the clinical outcomes of CB ablation compared with radiofrequency (RF) ablation in elderly patients with AF. METHODS: This was a single-center retrospective study of 305 patients older than 75 years with paroxysmal and persistent AF who underwent PVI between January 2012 and August 2017. Patients were matched according to propensity scores in a logistic regression model. The end point of this study was AF/atrial tachycardia recurrence at 12-month follow-up. RESULTS: In total, 198 patients (99 matched pairs) were analyzed. The ratio of paroxysmal AF was 83%, and the mean age was 78 ± 2 years. The mean procedure time was significantly lower in the CB group (134 ± 62 minutes vs 190 ± 51 minutes; P < .001). There was no significant difference between the groups in terms of success rate at 12 months after the procedure (CB 80.5% vs RF 79.4%; P = .72) or incidence of complications (CB 12% vs RF 16%; P = .80). Kaplan-Meier estimates revealed no significant difference between clinical outcomes after PVI with a CB or RF for elderly patients with non-pulmonary vein foci that were all successfully ablated (CB 68.8% vs RF 68.4% at 12 months; P = .835). CONCLUSION: The efficacy of PVI with a CB might be comparable to that of PVI with RF in AF patients older than 75 years and involve a shorter procedure time.