Outcomes in Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients.

RATIONALE: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for intensive care unit (ICU) management. OBJECTIVES AND METHODS: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015 and December 31, 2020 to 14 French ICUs. MEASUREMENTS AND MAIN RESULTS: One thousand one hundred and sixty-four patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented multiple organ dysfunction, including acute respiratory failure in 40% (n=461). Median SOFA was 6 (4-8). Invasive mechanical ventilation, renal replacement therapy and vasopressors were required in 438 (38%), 221 (19%) and 468 (41%) patients respectively. ICU mortality was 26% (302 deaths). Day-90, 1-year and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age >56 years (OR 2·0 [1·53-2·60], p<0·001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR 1·68 [1·17-2·40], p=0·005), corticosteroid-refractory acute graft-versus-host disease (OR 1·63 [1·38-1·93], p<0·001), need for vasopressors (OR 1·9 [1·42-2·55], p<0·001), and mechanical ventilation (OR 3·1 [2·29-4·18], p<0·001) were independently associated with day-90 mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (4 associated risk factors for mortality). CONCLUSIONS: Most critically ill Allo-HSCT recipients survive their ICU stay, including those requiring mechanical ventilation, with an overall day-90 survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with ≥ 2 risk factors for mortality.

Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.

T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events. Cytokine release syndrome (CRS) is the most common reaction and is largely confined to the first drug administrations during step-up dosage. Cytokine release syndrome should be distinguished from infusion related reaction by clinical symptoms, timing to occurrence, pathophysiological aspects, and clinical management. Other common reactions and adverse events with TCE are immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), infections, tumor flare reaction and cytopenias. The toxicity profiles of TCE and CAR-T cells have commonalities and distinctions that we sum-up in this review. As compared with CAR-T cells, TCE are responsible for less frequently severe CRS or ICANS. This review recapitulates terminology, pathophysiology, severity grading system and management of reactions and adverse events related to TCE.