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This study aimed to clarify the risk factors and prognosis associated with blood stream infection (BSI) in allogeneic hematopoietic cell transplantation (allo-HCT), and the relationship between BSI and acute graft-versus-host disease (aGVHD). This retrospective analysis included 11,098 patients in the Japanese national transplant registry. A total of 2172 patients developed BSI after allo-HCT, with 2332 identified pathogens. The cumulative incidences of BSI were 15.5% at 30 days and 20.9% at 100 days after allo-HCT. In a multivariate analysis, severe (grade III-IV) aGVHD was associated with a higher risk of BSI (vs. grade 0-I aGVHD: hazard ratio [HR] 3.34 [95% confidence interval (CI), 2.85-3.92; P < 0.001]). In a multivariate analysis, severe aGVHD before BSI was associated with a higher risk of overall mortality after BSI (vs. grade 0-I aGVHD: HR 2.61 [95% CI 2.18-3.11; P < 0.001]). In addition, BSI (vs. no-BSI: HR 1.20 [95% CI, 1.12-1.29; P < 0.001]) and severe aGVHD (vs. grade 0-I aGVHD: HR 1.97 [95% CI, 1.83-2.12; P < 0.001]) were independent risk factors for overall mortality after allo-HCT. In the setting of allo-HCT, severe aGVHD was associated with increases in both BSI incidence and post-BSI overall mortality. Furthermore, BSI was an independent risk factor for overall mortality.

Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) confers a dismal prognosis when treated with chemotherapy alone. Data on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes are limited. We retrospectively analyzed 4649 AML patients who received allo-HCT and were in complete remission. Outcomes of Ph+ AML (n = 30), intermediate-risk, and poor-risk AML patients were compared. The 3-year overall survival after allo-HCT was similar in intermediate-risk (62.7%; 95% CI: 61.0-64.3%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.42); however, it differed significantly between the poor-risk (49.7%; 95% CI: 45.9-53.4%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.049). Disease-free survival in Ph+ AML patients was comparable to that in intermediate-risk patients but better than that in poor-risk patients. Relapse rates were significantly lower in Ph+ AML patients than in other groups. Non-relapse mortality (NRM) rates were similar among groups. Multivariate analysis showed that Ph+ AML was not a significant predictor of poor prognosis in terms of overall survival, disease-free survival, relapse, and NRM. Our data showed better post-transplant outcomes for Ph+ AML patients than for those with poor-risk AML. Hence, allo-HCT could be a feasible treatment option for Ph+ AML patients.

The effects of ABO incompatibility on hematopoietic stem cell transplantation remain controversial. Large cohorts are required to obtain findings that allow for definite conclusions. We previously demonstrated poor overall survival and increased treatment-related mortality (TRM) in ABO-incompatible unrelated bone marrow transplantation (UR-BMT) performed during the period from 1993 to 2005. To improve our understanding of ABO-incompatible transplantation, we reanalyzed the effects of ABO mismatch in a UR-BMT cohort in Japan after 2000. Multivariate analyses for the 2000–2006 cohort showed that major ABO mismatch was associated with poor overall survival (HR, 1.211; 95% CI, 1.062 to 1.381; p = 0.004) and increased TRM (HR, 1.357; 95% CI, 1.146 to 1.608; p

We conducted a nationwide retrospective study to evaluate the prognostic influence of +1, der(1;7)(q10;p10) [hereafter der(1;7)] and ?7/del(7q) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndromes (MDS). In this database, 69 MDS patients with der(1;7), 75 with ?7/del(7q), and 511 with normal karyotype (NK) underwent allo-HSCT at advanced disease status. The 3-year overall survival (OS) and cumulative incidence of relapse (CIR) were 50.4 and 19.4% for those with der(1;7), 36.2 and 38.4% for ?7/del(7q),and 51.1 and 20.7% for NK, respectively. In the multivariate analysis, the presence of ?7/del(7q) correlated with a significantly shorter OS (HR [95% CI], 1.38 [1.00?1.89]; P = 0.048) and higher CIR (HR, 2.11 [1.36?3.28]; P = 0.001) than those with NK. There were 23 patients with der(1;7), 29 with ?7/del(7q), and 347 with NK who underwent allo-HSCT at early disease status.The 3-year OS and CIR were as follows: 47.3 and 9.5% for the der(1;7) group, 70.5 and 13.8% for ?7/del(7q), and 70.9 and 5.6% for NK,respectively. No significant differences were observed in OS and CIR among three groups. The impact of the loss of chromosome 7q on OS and CIR may differ based on its type and disease status after allo-HSCT for MDS., Bone Marrow Transplantation, 54(9), pp.1471-1481; 2019

The significance of low-dose total body irradiation (TBI) in HLA-mismatched reduced-intensity conditioning stem cell transplantation (RICT) remains unknown. We, retrospectively, evaluated the impact of low-dose TBI in patients with hematological malignancies who received first RICT from ≥1 antigen-mismatched donors between 2004 and 2014. Of the 575 patients, 361 patients received low-dose TBI (2 or 4 Gy). There were no significant differences in neutrophil engraftment or platelet recovery between TBI and non-TBI groups. The benefit of low-dose TBI on neutrophil engraftment was not observed in any subgroups. Low-dose TBI was not associated with decreased secondary graft failure. Suppressed mixed chimerism and autologous hematopoiesis by low-dose TBI was observed. There were no significant differences in cumulative incidences of acute GVHD or nonrelapse mortality rates in either group; however, low-dose TBI improved overall survival (OS), especially in patients with high-risk disease, multi-HLA mismatch, and fludarabine/busulfan conditioning. Multivariate analysis demonstrated that low-dose TBI was an independent prognostic factor for OS. Compared with the non-TBI group, 4 Gy TBI, but not 2 Gy TBI, was associated with increased acute GVHD and reduced relapse. These findings suggest that low-dose TBI may be beneficial for patients at high risk for relapse in HLA-mismatched RICT.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994–2006 and 2007–2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P

The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P