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Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy approved for the treatment of hematologic malignancies. This therapy leads to a variety of immunologic deficits that could place patients at risk for invasive fungal disease (IFD). Studies assessing IFD in this setting are limited by inconsistent definitions and heterogeneity in prophylaxis use, although the incidence of IFD after CAR T-cell therapy, particularly for lymphoma and myeloma, appears to be low. This review evaluates the incidence of IFD after CAR T-cell therapy, and discusses optimal approaches to prevention, highlighting areas that require further study as well as future applications of cellular therapy that may impact IFD risk. As the use of CAR T-cell therapy continues to expand for hematologic malignancies, solid tumors, and most recently to include non-oncologic diseases, understanding the risk for IFD in this uniquely immunosuppressed population is imperative to prevent morbidity and mortality.

BACKGROUND: In fall 2020, the Food and Drug Administration issued emergency use authorization for monoclonal antibody (mAb) therapies for outpatients with COVID-19. The Commonwealth of Massachusetts issued guidance outlining the use of a reserve system with a lottery for allocation of mAbs in the event of scarcity that would prioritize socially vulnerable patients for 20% of the infusion slots. The Mass General Brigham health system subsequently implemented such a reserve system. RESEARCH QUESTION: Can a reserve system be deployed successfully in a large health system in a way that promotes equitable access to mAb therapy among socially vulnerable patients with COVID-19? STUDY DESIGN AND METHODS: We conducted a retrospective review of the operation of the reserve system for allocation of mAb therapies to identify how referrals moved through the allocation process and what proportion of patients who were offered and received mAb therapies were socially vulnerable. RESULTS: Notwithstanding multiple operational challenges, the reserve system for allocation of mAb therapy worked as intended to enhance the number of socially vulnerable patients who were offered and received mAb therapy. A significantly higher proportion of patients offered mAb therapy were socially vulnerable (27.0%) than would have been the case if the infusion appointments had been allocated using a pure lottery system without a vulnerable reserve (19.8%), and a significantly higher proportion of patient who received infusions were socially vulnerable (25.3%) than would have been the case if the infusion appointments had been allocated using a pure lottery system (17.6%) INTERPRETATION: Our health system experience demonstrates that a reserve system with a lottery for tiebreaking is a viable way to distribute scarce therapeutics when enhancing access for certain groups is desirable.

The dipole strength of 206Pb was studied below the neutron separation energy using photon scattering experiments at the HIGS facility. Utilizing the technique of nuclear resonance fluorescence with 100% linearly-polarized photon beams, the spins, parities, branching ratios and decay widths of excited states in 206Pb from 4.9 - 8.1 MeV have been measured. The new experimental information is used to reliably predict the neutron capture cross section of 205Pb, an important branch point nucleus along the s-process path of nucleosynthesis., SCOPUS: cp.p, info:eu-repo/semantics/published

Objectives: A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods: Patients (N=237) received 300mg of posaconazole iv twice daily on day 1, followed by 300mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400mg twice daily or 200mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (C-avg) and posaconazole trough levels (C-min). Results: Mean posaconazole C-min was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state C-min was 1090 ng/mL (day 10). Mean steady-state posaconazole C-avg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions: Intravenous posaconazole at 300mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk.

Objectives: A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods: Patients (N=237) received 300mg of posaconazole iv twice daily on day 1, followed by 300mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400mg twice daily or 200mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (C-avg) and posaconazole trough levels (C-min). Results: Mean posaconazole C-min was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state C-min was 1090 ng/mL (day 10). Mean steady-state posaconazole C-avg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatment-related adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions: Intravenous posaconazole at 300mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk.

Objectives: A two-part (Phase 1B/3), sequential, open-label, multicentre study evaluated the pharmacokinetics (PK) and safety of intravenous (iv) posaconazole given as antifungal prophylaxis to neutropenic patients with AML or myelodysplastic syndrome (MDS) or to recipients at risk of invasive fungal disease (IFD) after allogeneic HSCT. Methods: Patients (N=237) received 300mg of posaconazole iv twice daily on day 1, followed by 300mg of posaconazole iv once daily for 4-28 days. After at least 5 days, patients were randomly assigned to receive posaconazole oral suspension, 400mg twice daily or 200mg three times daily, to complete a 28 day treatment course. Primary PK parameters were steady-state average concentration over the dosing interval (Cavg) and posaconazole trough levels (Cmin). Results: Mean posaconazole Cmin was 1320 ng/mL (day 6) and 1297 ng/mL (day 8); steady-state Cmin was 1090 ng/mL (day 10). Mean steady-state posaconazole Cavg was 1500 ng/mL (day 10 or 14) and was similar in HSCT recipients (1560 ng/mL) and AML/MDS patients (1470 ng/mL). The most commonly reported treatmentrelated adverse events were diarrhoea (8%), nausea (5%) and rash (5%). IFD was reported in 3/237 patients (1%; 2 proven, 1 probable). Conclusions: Intravenous posaconazole at 300mg was well tolerated, resulted in adequate steady-state systemic exposure and was associated with a low incidence of IFD in this population at high risk., SCOPUS: ar.j, info:eu-repo/semantics/published

Photograph of Mrs. Sarah Hammond, youngest daughter of the Reverend Joseph Benson and sister of Ann Benson, aged 62. From Walker Family Scrapbook compiled by Peter Benson Walker. Private collection.

Photograph of Mrs. Sarah Hammond, youngest daughter of the Reverend Joseph Benson and sister of Ann Benson, aged 62. From Walker Family Scrapbook compiled by Peter Benson Walker. Private collection.

Photograph of Mrs. Sarah Hammond, youngest daughter of the Reverend Joseph Benson and sister of Ann Benson, aged 62. From Walker Family Scrapbook compiled by Peter Benson Walker. Private collection.

Photograph of Mrs. Sarah Hammond, youngest daughter of the Reverend Joseph Benson and sister of Ann Benson, aged 62. From Walker Family Scrapbook compiled by Peter Benson Walker. Private collection.