Patients with aggressive B-cell lymphoma receiving CAR T-cell therapy have a low rate of severe infections despite lack of universal antibacterial and antifungal prophylaxis.

OBJECTIVES: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL). METHODS: We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up. RESULTS: Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, ≥3 lines of treatment and pre-lymphodepletion neutropenia. CONCLUSIONS: Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach.

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.

Severe multiorganic flare of systemic lupus erythematosus successfully treated with rituximab and cyclophosphamide avoiding high doses of prednisone.

Both acute pancreatitis and diffuse alveolar haemorrhage are rare conditions associated with systemic lupus erythematosus (SLE). In this case report, a 23-year-old female with SLE was diagnosed with lupus-associated pancreatitis and, within a few days and despite initial therapy with pulse methyl-prednisolone, subsequently suffered an acute respiratory failure due to a diffuse alveolar haemorrhage. The patient was admitted to the intensive care unit and treatment was intensified with cyclophosphamide and rituximab, which shortly induced the complete remission of SLE with resolution of both clinical conditions. She completed treatment with six pulses of cyclophosphamide followed by azathioprine, hydroxychloroquine and prednisone at initial doses of 20 mg/d with rapid tapering to 5 mg/d, without relapse of the disease during the following year. This case can illustrate that, even in severe, life-threatening SLE flares, it is possible to avoid high-dose prednisone, which has been associated with severe side effects, including infections. Acute pancreatitis and diffuse alveolar haemorrhage are rare conditions caused by SLE. DAH can be a life-threatening complication, with an early mortality of at least 50%. When facing such severe SLE activity, there is a general tendency to use high doses of prednisone as the initial therapy, maintaining such high doses for long periods of time, even after the clinical situation has subsided. We report a case of a young woman with SLE, suffering from acute pancreatitis and diffuse alveolar haemorrhage, who was successfully treated with pulse methyl-prednisolone, hydroxychloroquine, cyclophosphamide and rituximab, combined with medium doses of prednisone.