Tatsuya Konishi

Drug-induced immune thrombocytopenia (DITP) caused by ampicillin (ABPC) is rarely reported. An 87-year-old woman developed severe thrombocytopenia on postoperative day 3 during treatment with multiple drugs, including ABPC, for chronic periprosthetic infection following total knee arthroplasty. Although the platelet counts were unresponsive to oral prednisolone and intravenous immunoglobulin, they recovered promptly after the discontinuation of ABPC. Flow cytometry demonstrated ABPC-dependent IgG binding to healthy donor platelets. This is the first report to confirm ABPC-dependent platelet-reactive IgG using flow cytometry, thereby expanding the diagnostic tools for suspected DITP and highlighting the need for early recognition, prompt drug withdrawal, and appropriate supportive care.

To diagnose HIV-associated neurocognitive disorders (HAND), several neuropsychological test batteries have been used in various studies and countries. In Japan, the Co-developing Comprehensive Neuropsychological Test Battery (CoCoBattery) was developed during a nationwide study conducted between 2014 and 2016 (the J-HAND study) to explore the prevalence of HAND and has been widely used thereafter. It consists of 14 tests covering eight key cognitive domains: language, attention/working memory, executive function, learning, memory, information-processing speed, visuospatial construction, and motor skills. However, some cases have been difficult to classify in terms of HAND severity due to the lack of subjective impairment assessments in CoCoBattery. Therefore, we added cognitive screening questions to CoCoBattery (CoCoBattery-Plus) and compared the results among 103 HIV-positive individuals. Using the original battery, 10 cases were diagnosed with HIV-associated dementia (HAD), 13 with mild neurocognitive disorder (MND), 39 with asymptomatic neurocognitive impairment (ANI), and 41 with no HAND. In contrast, using the new battery, four individuals who were previously unaware of cognitive impairment reported subjective complaints in response to the questions, leading to diagnostic changes: one case from ANI to HAD and three from ANI to MND. The final diagnoses were 11 HAD, 16 MND, and 35 ANI, corresponding to a reclassification rate of 3.9%. Subjective complaints are a crucial component in determining the severity of HAND, and we anticipate that CoCoBattery-Plus will enable more accurate HAND diagnosis.

Although bispecific antibody (BsAb) treatment is a valuable therapeutic option for post chimeric antigen receptor (CAR)-T cell therapy against relapsed/refractory large B-cell lymphoma, it remains to be clarified why it is still effective after intensive T-cell redirection therapy. Recently, the therapeutic potential of bystander CD8 ⁺ T cells in the field of cancer immunotherapy have been discussed. In this study, we have shown a clinical impact where bystander CAR-negative CD8 ⁺ T cells from a CAR-T cell product have a potential to augment immune responses of BsAb therapy through a case with relapsed diffuse large B-cell lymphoma after CD19 CAR-T cell therapy. T cells in a CAR-T-cell product dominantly showed central and effector memory T cells, and such T-cell phenotypes in peripheral blood significantly increased after CAR-T cell therapy. Furthermore, chronological T-cell receptor-β repertoire analyses for both CD8 ⁺ T cells and CD4 ⁺ T cells suggested that product-derived bystander CAR ⁻ CD8 ⁺ T cells successfully existed in a relapsed lymph node and expanded in the body after BsAb therapy. Further analyses are necessary, but our findings might help to explain the mechanisms and benefits of this sequential approach and strengthen the sequence of CAR-T cell therapy prior to BsAb therapy.

Background Deep vein thrombosis (DVT) is a common complication in cancer patients associated with significant morbidity and mortality. D-dimer is a widely used screening tool for suspected DVT; however, its accuracy may be influenced by body mass index (BMI). We evaluated whether BMI modified the diagnostic utility of D-dimer levels in patients with cancer and DVT. Methods We retrospectively analyzed 439 patients with newly diagnosed solid cancers suspected of having DVT between January 2013 and December 2020. DVT was confirmed or excluded by using computed tomography or echography. D-dimer was measured, and patients were classified by BMI as low- (< 18.5 kg/m²), normal- (18.5–24.9 kg/m²), or high-BMI (≥ 25.0 kg/m²). D-dimer levels, positive and negative predictive values (PPV and NPV), and overall survival (OS) were compared. Results Of 439 patients, 175 (39.9%) had DVT. BMI did not differ significantly between the DVT-positive and DVT-negative patients. In the normal and high BMI groups, D-dimer levels were significantly higher in patients with DVT than those without (p < 0.01), whereas patients with a low BMI did not show this difference (p = 0.12). Using a 1 µg/mL cut-off, PPV was 32% in low-, 52% in normal-, and 49% in high-BMI patients; NPV was 83%, 91%, and 97%, respectively. OS did not differ among the BMI groups, and no deaths were directly related to DVT. Conclusion Diagnostic performance of D-dimer level may diminish in underweight patients with cancer. Clinicians should carefully interpret the D-dimer levels in low-BMI populations and consider additional diagnostic strategies.

Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m²) was administered for 7 days, followed by GO (3 mg/m²) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies.