Clinical Outcome of Aspergillus-Specific Cytotoxic T Lymphocytes for Refractory Invasive Aspergillosis in Patients with Hematological Malignancies.

Invasive aspergillosis has high mortality in patients with hematological malignancies after chemotherapy or allogeneic stem cell transplantation (SCT) due to usually low response rate to current antifungal agents and relatively poor tolerance to the toxicities of the antifungal medicines. In this pilot clinical study, we explore to manage the patients with refractory invasive aspergillosis with aspergillus-specific cytotoxic T lymphocytes (aspergillus CTL). Ten patients who were either no longer response to antifungal medicines or have to stop antifungal agents due to severe toxicities were included in this clinical study. Diagnosis are ALL (2 cases), AML (5 cases), and CML (3 cases). The median age was 37 (10 to 62) years old. Seven of them received allogeneic SCT (unrelated 3 cases, haploidentical 3 cases, identical sibling 1 case), and 3 patients were after chemotherapy. Aspergillus CTLs were either donor origin (5 cases) or patient origin (5 cases) if original donor was not available. Patients received 1 to 3 infusions of aspergillus CTLs. The median CTLs infused were 3.61 (0.28–40.00) x 10⁵/kg. No infusion-related reactions were noted. No pre-existed graft-versus-host disease deteriorated. With aspergillus CTL therapy, one of them (10%) achieved complete response, 6 patients (60%) improved significantly, 1 case was stable, and 2 patients became worse. Our preliminary data has shown that aspergillus-specific cytotoxic T lymphocyte is a safe and promising mean to manage refractory invasive aspergillosis in patients with hematological malignancies.