Yusuke Komiya's research while affiliated with Jichi Medical University and other places

The optimal bridge strategy at the decision for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndrome (MDS) is unclear. We performed a prospective observational study in which 110 patients with MDS who were decided to undergo HSCT were enrolled. Among these 110 patients, 77 patients were enrolled in this study within 1 month from the decision for HSCT. Among these 77 patients, 13 patients had a human leukocyte antigen (HLA)-matched sibling, 54 patients started an unrelated donor search, and the other 10 patients directly selected cord blood (CB) at the decision for HSCT, and 13 (100%), 38 (70.4%), and 9 (90%) patients actually underwent HSCT within 1 year, respectively. The overall survival (OS) at 1 year from their enrollment was 70.9%, and the selection of azacitidine use at the decision for HSCT was not associated with OS. Among 60 of the 77 patients who actually underwent HSCT within a year from their enrollment, a lower relapse rate after HSCT was observed in those who selected CB at the decision to undergo HSCT. However, this preferable effect of CB selection disappeared when patients who were enrolled in this study in > 1 month from the decision for HSCT were additionally included in the analyses. In conclusion, the selection of bridge strategy at the decision for HSCT did not affect outcomes in patients with MDS. The immediate performance of HSCT may be associated with better outcomes.

High-dose cytarabine (HD-AraC) or anthracycline-containing chemotherapies are used as post-remission therapy for acute myeloid leukemia (AML) patients. However, it remains unclear which regimen would be better as post-remission therapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thus, we compared the incidence of cardiac events and event-free survival (EFS) after allo-HSCT at two Japanese hospitals between HD-AraC and anthracycline-containing post-remission therapy to clarify the safety of post-remission therapy. Of a total of 132 patients, 68 received HD-AraC (HD-AraC group) and 64 received anthracycline-containing chemotherapy (ANT group). HD-AraC was preferentially selected for core-binding factor AML patients (p = 0.008). The median cumulative anthracycline dose was 115.2 mg/m² in the HD-AraC group and 318.7 mg/m² in the ANT group (p < 0.0001). Cardiac events were observed in 18 (13.6%) patients during the follow-up period. The 3-year cumulative incidence of cardiac events was 9.1% in the HD-AraC group and 11.0% in the ANT group (p = 0.70). EFS at 3 years after allo-HSCT was 40.9% in the HD-AraC group and 39.6% in the ANT group (p = 0.51). In conclusion, incidence of cardiac events did not differ significantly between post-remission therapy regimens in AML patients who underwent allo-HSCT.

We hypothesized that systemic corticosteroid administration would be safely avoided not only in grade I acute graft-versus-host disease (GVHD) but also in selected patients with grade II acute GVHD limited to the skin (grade IIs GVHD). We retrospectively evaluated risk factors for subsequent GVHD progression, defined as the involvement of other organs or progression to grade III to IV GVHD, in 50 patients with acute GVHD of grade IIs at its onset. Sixteen patients received systemic corticosteroid administration before GVHD progression. The cumulative incidence of GVHD progression at 28 days from the onset of grade IIs GVHD was 24%. Twenty-five patients did not require systemic corticosteroid administration throughout the entire episode of acute GVHD. Systemic corticosteroid administration before GVHD progression did not affect GVHD progression, chronic GVHD, or non-relapse mortality. Early onset (less than 26 days from transplantation) of grade IIs GVHD was identified as the only statistically significant risk factor for GVHD progression (hazard ratio 6.73, 95% confidence interval 1.5–31.1, P = 0.01). In conclusion, avoiding systemic corticosteroid administration for selected patients with grade IIs GVHD before GVHD progression did not compromise the transplantation outcomes. Patients with early-onset grade IIs GVHD were at high risk for GVHD progression.

While positive cytotoxic crossmatch (XM) has been reported to predict graft failure, mainly in solid organ transplantations, the significance of positive XM in allogeneic hematopoietic cell transplantation (HCT) remains to be elucidated. We retrospectively assessed the impact of positive XM on neutrophil engraftment in 41 patients who received HCT from a human leukocyte antigen (HLA)-mismatched related donor. XM was positive in 22 patients. Among these 22 patients, 6 were also positive for anti-HLA antibody, while only 1 was positive for donor-specific anti-HLA antibody. The cumulative incidence of engraftment at day 28 was 89.5% in patients with negative XM vs 59.1% in those with positive XM (P=0.08). Especially, positive B-cell warm XM was significantly associated with a lower probability of engraftment at day 28 (46.7% vs 88.5%, P=0.04). In a multivariate analysis, both positive XM and positive B-cell warm XM were significantly associated with a delayed achievement of engraftment (HR 0.46 and P=0.02, HR 0.41 and P=0.01, respectively). There was no significant difference in the achievement of engraftment between those with and without detection of anti-HLA antibodies. In conclusion, positive XM might be associated with a delayed neutrophil engraftment in HCT from HLA-mismatched related donors.

We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance.

Background: We examined the clinical characteristics and predictive factors for mortality in coryneform bacteria bloodstream infection in hematological patients. Methods: We searched for hematological patients who had positive blood cultures for coryneform bacteria at our center between April 2007 and January 2016. Patients with definite bloodstream infections were included. We started species identification in April 2014. Results: Twenty of twenty-eight cases with a positive blood culture for coryneform bacteria were regarded as definite infections. Sixteen and two patients were allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients, respectively. Corynebacterium striatum was identified in all nine of the cases tested and one patient was co-infected with Corynebacterium amycolatum. None of the patients died directly due to coryneform bacteria infection. The survival rates at 30, 60 and 180 days were 100%, 73.7% and 51.3%, respectively. Causes of mortality included progression of the underlying disease (n = 6), other infections (n = 4) and HSCT complications (n = 2). Mixed infection (hazard ratio (HR) 5.47, 95% confidence interval (CI) 1.30-23.0), renal impairment (HR 6.31, 95% CI 1.06-37.4) and absence of a central venous (CV) catheter at the onset (HR 6.39, 95% CI 1.04-39.45) were identified as predictive factors for mortality. Conclusion: Most of the coryneform bacteria bloodstream infections occurred in HSCT recipients. Contamination seemed to be less common when coryneform bacteria were detected in blood in hematological patients. Although coryneform bacteria bloodstream infection seemed to mostly be manageable, the prognosis was not desirable, particularly in patients with mixed infection, renal impairment and absence of a CV catheter.

The patient was a 62-year-old woman with CD5⁺ diffuse large B-cell lymphoma. Treatment with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) was started. On the eleventh day of the third cycle, headache and low grade fever developed. Her consciousness gradually deteriorated. Seven days after symptom onset, she was brought to the emergency department of our hospital. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 25/μl, and a protein level of 188 mg/dl. Antibacterial and antiviral agents were administered based on a diagnosis of acute meningitis. She showed no improvement. We performed another lumbar puncture and intrathecal chemotherapy, a combination of methotrexate and dexamethasone, was administered because we suspected central nervous system involvement of lymphoma. She showed transient improvement. On day 12, we started the R-MPV regimen (rituximab, methotrexate, procarbazine, and vincristine). However, fever and disturbance of consciousness persisted. On day 20, we empirically started anti-tuberculosis treatment. Four days later, tubercle bacilli were confirmed by CSF culture after a 23-day incubation. We ultimately confirmed a diagnosis of tuberculous meningitis. Impaired cellular immunity in lymphoma patients increases the risk of tuberculosis. It is important to consider tuberculous meningitis in the differential diagnosis of a lymphoma patient presenting with meningitis.

Secondary failure of platelet recovery (SFPR), a late decrease in the platelet count following primary platelet recovery that is not due to relapse or graft rejection, occasionally occurs after allogeneic hematopoietic stem cell transplantation (HSCT). The risk factors and impact of SFPR on transplant outcomes are not well known in the clinical setting. Therefore, we retrospectively evaluated 184 adult patients who underwent their first allogeneic HSCT and achieved primary platelet recovery. The cumulative incidence of SFPR, defined as a decrease in the platelet count to below 20,000/µL for more than 7 days, was 12.2% at 3 years, with a median onset of 81 days (range 39-729) after HSCT. Among patients who developed SFPR (n=23), 19 (82.6%) showed recovery to a sustained platelet count of more than 20,000/µL without transfusion support, and the median duration of SFPR was 23 days (range, 7-1048 days). A multivariate analysis showed that in vivo T-cell depletion (hazard ratio [HR], 6.92; 95% confidence interval [CI], 2.31-20.7; P < 0.001), grade II-IV acute graft-versus-host disease (HR, 3.99; 95% CI, 1.52-10.5; P = 0.005), and the use of ganciclovir or valganciclovir (HR, 2.86; 95% CI, 1.05-7.77; P = 0.039) were associated with an increased risk for SFPR. The occurrence of SFPR as a time-dependent covariate was significantly associated with inferior overall survival (HR, 2.29; 95% CI, 1.18-4.46; P = 0.015) in a multivariate analysis. These findings may help to improve the management and treatment strategy for SFPR.