Published papers

After allogeneic hematopoietic stem cell transplantation (HSCT), human herpesvirus-6 (HHV-6) can cause serious central nervous system (CNS) disorder and typically presents as encephalitis. Another manifestation of HHV-6 is myelitis, which has not been fully evaluated. In this study, we retrospectively analyzed 19 patients who developed HHV-6 myelitis after allogeneic HSCT. Median onset was 20 days after transplantation (range, 13–31), with a cumulative incidence of 4.1% at day 40 after transplantation. Median age at transplant was 50 years (range, 17–61). Median copy number of HHV-6 DNA was 3000 copies/ml in cerebrospinal fluid (CSF; range, 200–100,000). The most common symptoms were pruritus, pain of the extremities/back, and numbness. Three patients subsequently developed encephalitis in the clinical course of myelitis; their HHV-6 copy numbers in CSF had been higher than 10,000 copies/ml at the onset of myelitis. Antiviral agents were initiated shortly after onset in all patients, resulting in recovery. These results suggest that myelitis would be an important subtype of HHV-6-associated CNS disorders after allogeneic HSCT, whose prognosis could be favorable by an early intervention. Transplant physicians should recognize early posttransplant neurological symptoms such as pruritus, pain, or numbness as possible signs of HHV-6 myelitis, which could also progress to encephalitis.

A difference in clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH) among different races has been suggested. The aim of this study was to clarify whether the clinical characteristics of patients with PNH in the International PNH Registry differ by ethnic background. Patients, who were eculizumab naïve at baseline and had ≥ 1% PNH clone size, were eligible for this analysis. Totally, 1793 patients were enrolled and divided into two cohorts, Asian (N = 246) and non-Asian (N = 1547). The Asian cohort was further divided into Asians in Asia cohort (N = 202) and Asians in non-Asia cohort (N = 44), based on geographical region. The Asian cohort had significantly higher PNH clone size in granulocytes, higher lactate dehydrogenase levels, and lower hemoglobin levels. However, the frequencies of symptoms including abdominal pain, backache, easy bleeding, fatigue and headache at baseline were significantly lower in the Asian cohort. The proportion of patients with a history of thromboembolism (TE) was significantly lower in the Asian than in the non-Asian cohort (3.6% vs. 8.9%, P < 0.01); however, there was no difference between Asians in Asia and Asians in non-Asia (3.3% vs. 4.9%, P = 0.61). These findings suggested that genetic factors may play a stronger role in developing TE than lifestyle factors in PNH patients.

Background: Human herpesvirus 6 (HHV-6) causes life-threatening central nervous system disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent studies implicated CD134 as a specific receptor of HHV-6B and demonstrated that its expression levels in CD4-positive T cells after allo-HSCT could be related to the reactivation of HHV-6. We prospectively evaluated the relationship between HHV-6 reactivation and CD134+ T cells in the recipients of allo-HSCT. Methods: HHV-6 viral load in plasma was quantitatively measured weekly after allo-HSCT by digital polymerase chain reaction in 34 patients. The ratio of CD134 in CD4+ T cells (CD134/CD4 ratio) was serially measured by flow cytometry before and after transplantation. Results: HHV-6 reactivation was detected in 23 patients (68%). The CD134/CD4 ratio before conditioning was significantly higher in patients with HHV-6 reactivation than in those without (median, 3.8% vs 1.5%, P <. 01). In multivariate analysis, a higher CD134/CD4 ratio before conditioning was significantly associated with the incidence of HHV-6 reactivation (odds ratio, 10.5 [95% confidence interval, 1.3-85.1], P =. 03). Conclusions: A higher CD134/CD4 ratio before conditioning was associated with a higher risk of HHV-6 reactivation, suggesting that the rate may be a promising marker for predicting HHV-6 reactivation after allo-HSCT.

Background: Immunoglobulin (Ig) G2 subclass deficiency is known to be associated with recurrent bacterial respiratory infections caused by capsulated bacteria and is found mostly in pediatric patients. However, its impact after allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully assessed. Methods: We retrospectively evaluated the relationship between IgG2 subclass levels and bacterial pneumonia in 74 adult patients who survived longer than 2 years after allogeneic HSCT. Results: During the evaluation period, nine patients developed bacterial pneumonia. The median IgG2 level was significantly lower in patients with an infectious episode than in those without (143 mg/dL vs 287 mg/dL; P < 0.01). In multivariate analysis, a history of rituximab therapy and cord blood as a stem cell source were significantly associated with decreased levels of both IgG2 and IgG2/IgG ratios (P < 0.05). Conclusions: Suboptimal serum IgG2 levels could increase susceptibility to late-onset bacterial pneumonia after allogeneic HSCT. IgG2 levels should be considered carefully, especially in patients receiving cord blood transplantation and/or rituximab treatment.