Published on October 09, 2026
A Phase 1 Trial of CD123-Directed Chimeric Antigen Receptor T-Cell Therapy in Adults With Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm
by Alex Kadhim
A case report from the University of Kansas Medical Center highlights how a documented drug intolerance mislabeled as an allergy can leave a profoundly immunosuppressed cancer patient without coverage against a lethal parasite. Published in ASM Case Reports, this is the first description of hemophagocytic lymphohistiocytosis (HLH) triggered by toxoplasmosis during tumor-infiltrating lymphocyte (TIL) therapy, and is the fifteenth reported case of concurrent toxoplasmosis and HLH overall.
TIL therapy combines lymphodepleting chemotherapy with interleukin-2 (IL-2) and reliably produces grade 4 lymphopenia, yet prophylaxis guidance for this modality lags behind that written for chimeric antigen receptor T-cell therapy. Toxoplasma gondii persists as latent tissue cysts that reactivate when T-cell surveillance fails. The authors describe a 68-year-old man with metastatic melanoma who had received pembrolizumab, followed by nivolumab and relatlimab, before fludarabine and cyclophosphamide lymphodepletion and TIL infusion on Day 0. Trimethoprim-sulfamethoxazole prophylaxis had been stopped after five tablets were administered for gastrointestinal symptoms, recorded as a sulfonamide allergy without formal testing, leaving only inhaled pentamidine, which has no anti-Toxoplasma activity.
On Day +95 he presented with an altered mental status and fever (39.3°C), with laboratory findings including pancytopenia (absolute lymphocyte count 0.19 k/µL), fibrinogen 44 mg/dL, ferritin above 30,000 ng/mL, triglycerides 410 mg/dL, aspartate aminotransferase 368 U/L, and soluble CD25 at 6,979.4 pg/mL against a normal range of 175.3 to 858.2. His HScore of 283 corresponded to a greater than 99% probability of HLH, and a bone marrow biopsy showcased bradyzoites, tachyzoites, pseudocysts, and hemophagocytosis. The cerebrospinal fluid Toxoplasma polymerase chain reaction returned as 13,700 copies/mL, serum IgG was positive with negative IgM, and brain magnetic resonance imaging exhibited targetoid enhancing lesions. A CD4 count of 231 cells/µL six weeks post-infusion was observed, which was above the HIV-derived 200 cells/µL threshold, and had prompted deferral of dapsone. Pyrimethamine, sulfadiazine, and leucovorin were started, but the patient progressed into shock and comfort measures were thereby performed. The authors conclude that HIV-derived CD4 thresholds should not govern prophylaxis in non-HIV immunosuppression.
Reference:
Odeh T, Quach P, Mostofizadeh A, et al. Toxoplasmosis-associated hemophagocytic lymphohistiocytosis during tumor-infiltrating lymphocyte therapy. ASM Case Rep. 2026;2(5). https:doi.org/10.1128/asmcr.00070-26
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