Search

We report six cases of autoimmune acquired coagulation factor VIII deficiency, which is a rare bleeding disorder. It is an autoimmune disease, however, there are various causes. We experienced cases with malignancy, co-exist with another autoimmune disease, pregnancy, and unknown epidemiology with repeated bleeding episode. All patients were controlled the acute bleeding phase and they have been under treatment with immunosuppression.

We report the case of a man who developed myelodysplastic syndrome (MDS) and refractory cytopenia of unilineage dysplasia, 5 months after aortic valve replacement surgery. He also developed fever of unknown origin. After bone marrow- and other laboratory examinations, he was diagnosed with tuberculosis.

A 63-year-old man was diagnosed with a rare variant of acute promyelocytic leukemia (APL) with t(4;17)(q12; q21) that showed atypical morphological features and two different clinical symptoms. He was started on standard induction chemotherapy for acute myeloid leukemia, which decreased myeloblast numbers; however, APL-like blasts remained. He then received a salvage therapy that added all-trans retinoic acid (ATRA). After ATRA commenced, APL-like blasts disappeared and cytogenetic analysis became normal. However, myeloblasts subsequently increased, and he became resistant. In summary, this patient exhibited two different clinical courses of acute myeloid leukemia and APL.

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. Progress has recently been made in the pathological classification of PTLD. However, the clinical course has not been clarified because of the rarity of this disease. We experienced a case of PTLD with a fulminant clinical course. The patient had been under longterm immunosuppressive treatment for aplastic anemia. He received related allogeneic hematopoietic stem cell transplantation. Soon after transplantation, he developed PTLD. According to the guidelines, we reduced immunosuppression. However, the disease course was so fulminant that there was no time for the patient to respond, and he died of multi-organ failure. There may be various clinical types of PTLD, which may include some fulminant cases. In such a case, it is not sufficient to reduce immunosuppression. The patient should be carefully observed and an appropriate individual treatment should be chosen.

A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents. In the current study, patients with hypercalcemia and bone disease showed a significantly worse prognosis, whereas anemia and renal failure showed no difference in survival. Novel agents used for treatment of patients with renal failure suggested a favorable outcome compared with conventional therapy. Bone disease was the most common factor and may have the strongest prognostic value in symptomatic myeloma patients using novel agents.

Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations. Antibody profiling of six groups stratified by antibody titer and the remaining neutralizing antibodies was also performed to study the dynamics of neutralizing antibodies against SARS-CoV-2 and the changes in antibodies against microbial antigens. The results showed that changes in antibodies against microbial antigens other than SARS-CoV-2 antigens were extremely limited after COVID-19 vaccination. In addition, antibodies against a staphylococcal complement inhibitor have been identified as microbial antigens that are associated with increased levels of neutralizing antibodies against SARS-CoV-2. These antibodies may be a predictor of the maintenance of neutralizing antibodies following the administration of a COVID-19 mRNA vaccine.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19–2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19–3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Intensive vaccination is recommended for populations more vulnerable to COVID-19 infection, although data regarding the built of immunity after vaccination for dialysis patients are lacking. This prospective, observational cohort study of maintenance hemodialysis patients examined IgG antibody levels against the SARS-CoV-2 spike (S1) protein, neutralizing activity, and interferon gamma levels after the third dose of the BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine. Humoral immunity was repeatedly measured for up to two months. The study includes 58 patients on hemodialysis. Median neutralizing antibodies reached a maximum at 56 and 9 days after booster vaccination with BNT162b2 and mRNA-1273, respectively. The median IgG antibody titer reached a maximum of 3104.38 and 7209.13 AU/mL after 16 days of booster dose, and cellular immunity was positive in 61.9% and 100% of patients with BNT162b2 and mRNA-1273 vaccination, respectively. By repeating the measurements over a period of two months, we clarified the chronological aspects of the acquisition of humoral immunity in dialysis patients after a booster COVID-19 vaccination; most dialysis patients acquired not only humoral immunity, but also cellular immunity against SARS-CoV-2. Future research should investigate the continued long-term dynamics of antibody titers and cellular immunity after the third or further vaccinations, evaluating the need for additional vaccinations for hemodialysis patients.

Measuring long-term antibody titer kinetics and subsequent coronavirus disease 2019 (COVID-19) vaccinations are crucial for identifying vulnerable populations. Our aim was to determine the association between long-term antibody kinetics, including peak titers and factors, up to seven months post-second vaccination. A three-time antibody survey was conducted in 2021 among healthcare workers in Japan to investigate the changes in humoral immunity using chemiluminescence immunoassay. The study involved 205 participants who had received the second vaccine dose, completed the three-time survey, and were not infected with SARS-CoV-2. A latent growth curve model was used to identify factors affecting the peak titer and decreasing the antibody slope. Of the eligible participants, the mean titers of immunoglobulin G (IgG) against the spike (S) protein and the neutralizing activity 7 months after the second vaccination decreased to 154.3 (8.8% of the peak titer) and 62.1 AU/mL (9.5% of the peak titer), respectively. The IgG growth model showed that age significantly affected peak titers (p < 0.001); however, a significant difference was not found for the decreasing slope. Ultimately, aging adults had significantly low peak antibody titers; however, age was unrelated to the slope of log-transformed IgG against the S protein.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive a third dose of a coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. This study included participants who provided answers in the questionnaire about whether they had an intent to receive a third dose of a vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate over the booster vaccination were retrieved. Among the 2439 participants, with a mean (±SD) age of 52.6 ± 18.9 years, and a median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that participants of a younger age (OR = 0.98; 95% CI: 0.96–1.00) and with a higher antibody level (OR = 2.52; 95% CI: 1.27–4.99) were positively associated with hesitancy over the third vaccine. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had a significant impact on behavior regarding the third vaccination. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken with these groups that are likely to hesitate over the third vaccine, subsequently increasing booster contact rate.