Factors Associated with Neutralizing Antibody Responses following 2-Dose and 3rd Booster Monovalent COVID-19 Vaccination in Japanese People Living with HIV.

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.

Serum immunoglobulin G as a discriminator of infection in follicular lymphoma patients undergoing chemotherapy with bendamustine in combination with rituximab.

OBJECTIVES: Chemotherapy, including bendamustine, usually causes lymphocytopaenia and hypogammaglobulinaemia as side effects in patients with haematological malignancies. Therefore, the possibility has been considered that these immunological adverse events induced by bendamustine may lead to infectious diseases. However, lymphocytopaenia and/or hypogammaglobulinaemia have not yet been shown to have a statistically significant association with infection in cancer patients who receive bendamustine. METHODS: We retrospectively studied 27 patients with relapsed or refractory indolent follicular lymphoma who were treated with bendamustine and rituximab (BR). In order to elucidate relationships between immune-related laboratory parameters (i.e. peripheral blood leukocyte, neutrophil, lymphocyte and immunoglobulin G [IgG]) and infectious events, receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Infectious diseases occurred in 11 patients (11/27, 41%), including 3 (3/27, 11%) with severe diseases. The area under the ROC curve (AUC) showed that the lowest IgG level during and after BR discriminated infectious events (cut-off value, 603 mg/dL) with 81.8% sensitivity and 68.8% specificity (AUC, 0.76; 95% CI, 0.52-0.90). Furthermore, a multivariate regression analysis revealed that the minimal serum IgG value during and after BR therapy was the only variable that was significantly associated with infection (odds ratio, 8.29; 95% CI, 1.19-57.62; p value, 0.03). CONCLUSION: Serum IgG ≤603 mg/dL during and after BR therapy was independently associated with an increased risk of infection. The monitoring of serum IgG during chemotherapy may help to predict the development of infection in blood cancer patients undergoing chemotherapy with bendamustine in combination with rituximab.

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen. PATIENTS AND METHODS: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m2/day), doxorubicin (10 mg/m2/day), and vincristine (0.4 mg/m2/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6. RESULTS: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation. CONCLUSION: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.

[The Usefulness of the Scan with 67Ga-citrate to Assess the Therapeutic Effect on Pneumocystis pneumonia with HIV-1 Infection].

OBJECTIVE: Peumocystis pneumonia (PCP) is one of the common opportunistic infections with severe respiratory failure, and is sometimes life-threatening in patients with the acquired immunodeficiency syndrome. Although treatment for PCP is established, an appropriate treatment period has not been evaluated to clarify the risk factors for immune reconstitution inflammatory syndrome (IRIS) associated with PCP. METHOD: We retrospectively analyzed the clinical characteristics of risk factor, which are the treatment period for PCP, and 67Ga scintigraphy (Ga-S) at the 21st day from the start of the treatment for PCP, with 21 cases of PCP and HIV infection treated during 2005-2012 at Kyushu Medical Center. RESULT: The rate of residual uptake by Ga-S was assessed in 17 cases (81%). Four cases were diagnosed as being PCP-IRIS, and residual uptake by Ga-S was detected in all PCP-IRIS cases. The durations of the therapy were classified into three groups: 21 days, 28 days, and 35 days. All PCP-IRIS cases were treated in the period of 28 days. In contrast, in 11 cases that showed residual uptake by Ga-S, and were treated for PCP in 35 days, PCP-IRIS did not occur. Additionally, there were 4 cases in which residual uptake by Ga-S did not occur. They were treated with PCP for only 21 days, but did not show PCP-IRIS. CONCLUSION: In this study, we showed that Ga-S is useful to evaluate the therapeutic effect. Furthermore, we found that the occurrence of PCP-IRIS could be prevented with the early start of cART after 21 days treatment for PCP, when residual uptake by Ga-S after the first treatment for PCP was not detected. It may also be possible to start cART in the early phase after its treatment without the occurrence of PCP-IRIS with the appropriate additional treatment of PCP for 14 days. These guidelines for treatment of PCP in HIV-infected adults and adolescents have been recommended for the duration of 21 days since 1984. We propose that for the prevention of PCP-IRIS, it is nessecory to reconsider recommendation for the treatment duration of 21 days, and meanwhile to evaluate the treatment effect of PCP with Ga-S, because PCP resistance to sulfa drugs, namely are trimethoprim-sulfamethoxazole, is beginning to appear.

[CMV-induced duodenal papillitis in a patient with HIV-1 infection].

We present herein a case report of a 59-year-old patient with HIV-1 infection who developed a CMV-induced pseudotumor of the duodenum. The patient presented with oral pain and dysphagia. Physical examination revealed oral thrush. An EIA and a Western blot assay for antibodies to HIV were positive. His CD4-positive lymphocyte count was initially 49/microL with an HIV viral load of 2.6 x 10(5) copies/mL. Cytomegalovirus (CMV) reactivation was detected with the CMV antigenemia assay. He had CMV retinitis in both eyes with unilateral blurring. An endoscopic study revealed candida esophagitis, and a tumor-like lesion with an irregular ulcer at the papilla of Vater. Histological and immunohistochemical studies revealed a CMV-induced pseudotumor and severely inflamed duodenal mucosa with infiltration of CMV-positive cells. The patient was treated with oral valganciclovir and fluconazole for three weeks. As the oral thrush and retinitis showed improvement, he began antiretroviral therapy (ART), consisting of raltegravir and TDF/ FTC. One month later the patient's CD4-positive cells increased to 130/microL and the level of HIV-RNA decreased to 160 copies/mL, The CMV retinitis had transiently worsened because of an ART-induced inflammatory response, immune reconstitution inflammatory syndrome (IRIS). Six months after the ART initiation, an endoscopic study revealed that the esophagitis and the lesion at the papilla had improved. Biopsy showed no CMV-positive cells in the epithelium. The patient was now in a relatively healthy condition. CMV-induced pseudotumors of the duodenum are rare, and sometimes resemble malignancy. However, because this tomor responds to medical treatment physicians treating severely immunocompromised patients should be aware of its presentation and treatment.

[Transfusion-related acute lung injury during the treatment of EBV-associated hemophagocytic lymphohistiocytosis].

Transfusion-related acute lung injury (TRALI) is a severe pulmonary complication following blood transfusions. We experienced a case of possible TRALI during the course of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). A 19-year-old woman was admitted to our hospital suffering from fever and abdominal pain. Her laboratory data revealed pancytopenia, liver damage, coagulopathy, and a high titer of EBV-DNA. Computed tomography showed hepatosplenomegaly and bone marrow aspiration revealed hemophagocytosis and the proliferation of atypical lymphocytes. A diagnosis of EBV-HLH was made and plasma exchange was performed. Severe hypoxia due to pulmonary edema developed two hours after starting the plasma transfusion. Methylprednisolone pulse therapy and non-invasive positive pressure ventilation ameliorated her respiratory condition. Anti-HLA class I and II antibodies were detected in donor sera and a cross-match test between patient lymphocytes and donor plasma was positive. To the best of our knowledge, this is the first case report of TRALI complicated with EBV-HLH. It is possible that hypercytokinemia accompanied by HLH was associated with the onset of TRALI.