Search

The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p < 0.001), (2) delay the median time until initiation of CMV antigenemia-guided preemptive therapy (90 vs. 36 days, p < 0.001), (3) shorten the duration of anti-CMV preemptive treatment (21 vs. 25 days, p = 0.006), and (4) improve the overall survival rate at 180 days after transplant (80.4 vs. 73.0%, p = 0.033) with a trend of lower non-relapse mortality (8.9 vs. 14.9%, p = 0.052). Our findings demonstrate that prophylactic LMV treatment is highly effective in preventing the development of csCMV infection and ultimately reduces transplant-related mortality.

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.

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.

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

We studied the hematopoietic activity of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony-stimulating factor (G-CSF) using semisolid and long-term culture systems (LTC) in 5 normal individuals. Following 2 or 3 daily subcutaneous injections of G-CSF (filgrastim; 1.5 micrograms/kg), not only committed progenitors including CFU-GM, BFU-E, and CFU-Mix, but also long-term culture initiating cells (LTC-IC) were increased in the peripheral blood. When the cells derived from CFU-GM, BFU-E and CFU-Mix colonies were replated for secondary colony formation, a minor fraction of CFU-GM and CFU-Mix colonies formed after 3 days of G-CSF stimulation in vivo could produce secondary colonies. Moreover, the replating capacity of primary colonies from 5-week-old LTC initiated after 3 days of G-CSF stimulation was increased compared to that from 5-week-old LTC initiated in a 'steady-state'. These observations indicate that G-CSF can mobilize very primitive progenitors (LTC-IC) along with committed progenitors into the circulation and suggest that some of these G-CSF-mobilized progenitors may retain self-renewal capacity.