川瀬 孝和

It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio, .56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Objectives To compare remission status at completion of chemotherapy for multiple myeloma (MM) with changes in total diffusion volume (tDV) calculated from whole-body diffusion-weighted imaging (WB-DWI) and fat fraction (FF) of lumbar bone marrow (BM) by modified Dixon Quant (mDixon Quant) soon after induction of chemotherapy, and to assess the predictive value of MRI. Methods Fifty patients (mean age, 66.9 +/- 10.5 years) with symptomatic myeloma were examined before and after two cycles of chemotherapy. From WB-DWI data, tDV was obtained with the threshold for positive BM involvement. Mean FF was calculated from lumbar BM using the mDixon Quant sequence. At the completion of chemotherapy, patients were categorized into a CR/very good PR (VGPR) group (n = 15; mean age, 67.6 +/- 10.3 years) and a PR, SD or PD group (n = 35; mean age, 69.1 +/- 8.6 years). ROC curves were plotted to assess performance in predicting achievement of CR/VGPR. Results At second examination, serum M protein, beta(2)-microglobulin, and tDV were significantly decreased and hemoglobin, mean ADC, and FF were significantly increased in the CR/VGPR group and serum M protein was significantly increased in the PR/SD/PD group. The general linear model demonstrated that percentage changes in FF and M protein contributed significantly to achieving CR/VGPR (P = 0.02, P = 0.04, respectively). AUCs of ROC curves were 0.964 for FF and 0.847 for M protein. Conclusions Early change in FF of lumbar BM and serum M protein soon after induction of chemotherapy contributed significantly to prediction of CR/VGPR.

Some studies support the hypothesis that HLA genes and haplotypes evolved by natural selection through their protective abilities against specific infectious pathogens. However, very little is known regarding the impact of high-frequency HLA haplotypes on the risk of relevant infectious diseases among a given ethnic group. We evaluated the impact of high-frequency HLA haplotypes on cytomegalovirus (CMV) reactivation and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a Japanese population as a model of infectious disease that has coexisted with humans. A total of 21,127 donor-patient pairs were analyzed. HLA-A-B-DRB1 haplotypes were estimated using the maximum probability algorithm. Seven haplotypes with >1% frequency were defined as high-frequency haplotypes (HfliPs). Homozygotes of HfHP and heterozygotes had significantly lower risk of CMV reactivation and infection (hazard ratio [HR] = 0.88, P= .009 and HR = 0.93, P= .003, respectively) than homozygotes of low-frequency HLA haplotypes (LfHPs). In subgroup analyses of a different donor source, these associations were statistically significant in unrelated donor transplants. Finally, CMV risk for homozygotes and heterozygotes of each HfHP was compared with that of homozygotes of LfHPs. The 2 most predominant HfHP groups (A*24:02-B*52:01-DRB1*15:02 group and A*24:02-B*07:02-DRB1*01:01 group) had a significantly lower risk of CMV reactivation and infection (HR = 0.86, P < .001 and HR = 0.91, P= .033, respectively). Our findings suggest that HfHPs may be protective against CMV reactivation and infection and that increased care regarding CMV reactivation and infection may be necessary for patients with LfHP after allo-HSCT. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.