Infections in haematology patients treated with CAR-T therapies: A systematic review and meta-analysis.

A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for haematological malignancy. Meta-analysis of pooled incidence, using random effects model, was conducted. Cochran's Q test examined heterogeneity. 2678 patients across 33 studies were included in the primary outcome. Forty-percent of patients (95% CI: 0.33 - 0.48) experienced an infection of any grade. Twenty-five percent of infection events (95% CI: 0.16 - 0.34) were severe. Late infections were as common as early infections (IRR = 0.86, 95% CI: 0.38 - 1.98). All-grade infections, bacterial and viral infections were highest in myeloma patients at 57%, 37% and 28% respectively. Patients with NHL more commonly experienced late infections. Pooled rate of invasive candidiasis/yeast infections was 2% in studies utilizing anti-yeast prophylaxis. This review identified a high rate of all-grade infections, moderate rate of severe infections, and myeloma as a high-risk haematological group.

Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Bispecific antibody therapy, its use and risks for infection: Bridging the knowledge gap.

Relapsed haematological malignancies have a poor disease prognosis with current therapies. Bispecific antibodies (BsAbs) are becoming increasingly recognised for their efficacy in the treatment of these malignancies and are approved for the treatment of B-cell acute lymphoblastic leukaemia (B-ALL). BsAbs are manufactured to consist two variable chain fragments combined by a peptide linker amongst other structures to increase the half-life of the molecules. BsAbs function by bringing targeted tumour cells in close proximity of T-cells to allow killing via perforin and granzyme release. The increasing numbers of trials of BsAbs has highlighted their toxicity profile, including cytokine release syndrome (CRS), cytopaenia and hypogammaglobulinemia - which all increase risks for infection. The patterns and risks for infections with these novel agents remain unclear. This review article provides an overview of the risks of infection with various BsAbs platforms. A review of clinical trials reveals rates of infections amongst patients on BsAbs between 15 and 45% with a high proportion grade 3 severity or higher. A predominance of bacterial respiratory and line-related infections were identified amongst all haematological malignancies. In particular, high rates of febrile neutropaenia were identified in use of BsAbs in myeloid malignancy. Infection patterns identified in this review are utilised to inform infection prevention practice, including focused infection screening, line management, prophylaxis and vaccination strategies. Prophylaxis strategies against Pneumocystis pneumonia, herpes simplex and herpes zoster, candida and mould infections are considered, along with vaccination strategies against respiratory viral and bacterial infections. The long-term impacts of BsAbs on the immune system continue to be established.

Remote Device Interrogation Kiosks (ReDInK) - Pharmacy Kiosk Remote Testing of Pacemakers and Implantable Cardioverter-Defibrillators for Rural Victorians. A Novel Strategy to Tackle COVID-19.

BACKGROUND: In the era of COVID-19, travel restrictions and social distancing measures have changed the landscape for device interrogations of pacemakers and defibrillators for rural Victorians. Previously, device checks were performed infrequently in large volume, face-to-face rural clinics by visiting cardiologists and technicians. Access to remote areas and social distancing restrictions have made these clinics unfeasible to operate. The Cardiac Society of Australia and New Zealand (CSANZ) and Heart Rhythm Society (HRS) COVID-19 consensus statements have suggested the utilisation of remote monitoring to minimise the potential spread of COVID-19 infections between clinicians and high-risk patients. A novel solution to this challenge was the implementation of a remote device interrogation (RI) service located in two kiosks at two rural pharmacies. This service was termed Remote Device Interrogation Kiosks (ReDInK). AIM: This cross-sectional observational study aimed to describe the set-up process, safety and efficacy of RI and customer satisfaction of the ReDInK program. METHODS: Two-hundred-and-ninety-two (292) rurally located patients with implantable cardiac devices were identified via the cardiology department database. Of these, 101 (44%) were enrolled into the ReDInK program across two rurally located pharmacies between April and July 2020. RI was performed and download outcomes were reviewed. A customer satisfaction survey assessed attitudes towards the program and explored options of ongoing service application. RESULTS: Of 101 patients enrolled into ReDInK, 96 (95%) resulted in satisfactory device checks. Four (4) individuals failed-to-attend and one individual experienced technical download issues. Of the 96 satisfactory device checks, three required in-person follow-up for reasons including battery replacement, lead repositioning and in-person programming. No adverse events were reported. A satisfaction telephone survey was conducted with 81 (83%) participants enrolled in ReDInK. Seventy-one (71) individuals (88%) of those surveyed expressed satisfaction and 73 (90%) labelled the process as efficiently conducted. Sixty-nine (69) (85%) participants felt reassured that this service was established during the pandemic. However 47 (58%) participants reported they would still feel comfortable to undergo in-person reviews despite social distancing recommendations. CONCLUSIONS: With the COVID-19 pandemic posing restrictions to social distancing and reducing unnecessary in-person interaction, the ReDInK program emerges as an efficacious and safe solution for patients in rural Victoria. The program's widely positive reception and successful conduction in rural Victoria invites further opportunity for a wider application of similar programs, expanding its role to metropolitan areas.

The role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in assessment of complex invasive fungal disease and opportunistic co-infections in patients with acute leukemia prior to allogeneic hematopoietic cell transplant.

INTRODUCTION: Individuals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention. METHODS: Two distinct cases of pulmonary co-infection of rare fungal and bacterial pathogens are explored in severely immunocompromised individuals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long-term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long-term antimicrobials prior to transition to HCT. DISCUSSION: The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting. CONCLUSION: FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high-risk immunocompromised patients.