Severe Candida glabrata pancolitis and fatal Aspergillus fumigatus pulmonary infection in the setting of bone marrow aplasia after CD19-directed CAR T-cell therapy – a case report

Abstract

Background Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications. Case presentation We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC < 100/μl), G-CSF-refractory, and prolonged, lasting more than 50 days. The patient developed severe septic shock 3 weeks after CAR transfusion while receiving anti-fungal prophylaxis with micafungin. His clinical status stabilized with broad anti-infective treatment and intensive supportive measures. An autologous stem cell backup was employed on day 46 to support hematopoietic recovery. Although the counts of the patient eventually started to recover, he developed an invasive pulmonary aspergillosis, which ultimately lead to respiratory failure and death. Postmortem examination revealed signs of Candida glabrata pancolitis. Conclusions This case highlights the increased risk for fatal infectious complications in patients who present with profound and prolonged cytopenia after CAR T-cell therapy. We describe a rare case of C. glabrata pancolitis associated with multifactorial immunosuppression. Although our patient succumbed to a fatal fungal infection, autologous stem cell boost was able to spur hematopoiesis and may represent an important therapeutic strategy for DLBCL patients with CAR T-cell associated bone marrow aplasia who have underwent prior stem cell harvest.

Pulmonary infection in traumatic brain injury patients undergoing tracheostomy: predicators and nursing care

“…Suction sputum in time, try to avoid infection around the tracheal incision and damage to the mucous membrane of the respiratory tract to reduce bacterial migration [ 40 , 41 ]. Besides, adopt a reasonable posture, turn over and pat the back on time to avoid sputum accumulation is helpful to prevent pneumonia [ 42 – 44 ]. Furthermore, early nutritional supports are needed, and if necessary, infusion of plasma or albumin to improve the body's resistance to prevent and reduce the chance of nosocomial infection [ 45 ].…”

CD34+-selected stem cell boost can safely improve cytopenias following CAR T-cell therapy

“…This may be explained by the fact that CD19 + progenitor cells are present in the SCB 14 which may lead to activation of circulating CAR-T cells precipitating CRS. This has not been previously reported after autologous stem cell infusion to treat delayed count recovery post-CAR-T therapy in adult patients with lymphoma or myeloma [15][16][17] . Prolonged neutropenia and lymphopenia predispose patients to significant infections post CAR-T therapy 18 .…”

Infectious complications of CAR T-cell therapy: a clinical update

“… 21 , 29 , 31 One patient has died from severe Candida glabrata pancolitis and Aspergillus fumigatus pulmonary infection. 49 This was likely secondary to profound granulocyte colony stimulating factor (G-CSF) refractory neutropaenia lasting more than 50 days as well as prolonged high-dose corticosteroids for CRS.…”