Journal Article

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

Weigert, Oliver, Dreyling, Martin, Stemmler, Joachim, Rejeski, Kai, Subklewe, Marion, Dimitriadis, Konstantin, von Bergwelt-Baildon, Michael, Rudelius, Martina, Schmidt, Christian, Karschnia, Philipp, Schöberl, Florian, Kunz, Wolfgang G., Bücklein, Veit, Blumenberg, Viktoria, von Baumgarten, Louisa

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adverse events / Anemia, Aplastic - etiology / Anemia, Aplastic - therapy / Antibiotics / Antifungal agents / Antigens, CD19 - adverse effects / Antigens, CD19 - therapeutic use / Antiinfectives and antibacterials / Aplasia / Aspergillosis / Aspergillus fumigatus - isolation & purification / Autografts / Autopsy / Bacterial and fungal diseases / Bacterial infections / Bone marrow / Bronchoscopy / Candida glabrata / Candida glabrata - isolation & purification / Candidiasis / CAR T-cell / Case Report / Case reports / Case studies / CD19 antigen / Cell therapy / Cellular therapy / Cerebrospinal fluid / Complications and side effects / Consciousness / Corticoids / Corticosteroids / Cytokines / Diseases / Fatal Outcome / Fever / Fungal infections / Fungi / Fungicides / Granulocyte colony-stimulating factor / Hematopoiesis / Hematotoxicity / Humans / Immunosuppression / Immunosuppressive agents / Immunotherapy / Immunotherapy, Adoptive - adverse effects / Infections / Infectious Diseases / Internal Medicine / Invasive aspergillosis / Invasive Fungal Infections - etiology / Invasive Fungal Infections - microbiology / Invasive Fungal Infections - therapy / Lymphocytes T / Lymphoma / Lymphoma, Large B-Cell, Diffuse - therapy / Male / Medical Microbiology / Medicine / Medicine & Public Health / Micafungin / Middle Aged / Myelosuppression / Neutropenia / Parasitology / Patient outcomes / Patients / Pneumonia / Prophylaxis / Pulmonary aspergillosis / Respiratory failure / Risk factors / Septic shock / Stem cells / Transfusion / Tropical Medicine / Ulcerative colitis / Viral infections