Biology and Immunogenetics of Immune Effectors: Applications in Hematology and Cell Therapy

Immune effectors are the cells responsible for host response to cancer cells and germs. There is a stringent need to understand immune effectors biology to improve infectious disease management, particularly for patients affected by deep grade immunosuppression. During my research, I chose to investigate the role of Glucose-6-Phosphate Dehydrogenase (G6PD) on immune effectors biology, to evaluate its relevance for response to infectious agents. G6PD is a key enzyme of pentose-phosphate pathway, producing reducing power in the form of NADPH, that is essential for oxidative stress protection machinery. The typical manifestations of enzyme deficiency are acute hemolytic anemia (AHA) following exposure to drugs or food and neonatal jaundice. The enzyme is expressed in all cells, but typical manifestations are related to enzyme deficiency in red cells. G6PD deficiency impact on white cells is less studied; some authors postulated that enzyme deficiency confers susceptibility to infections, but evidences are controversial. I tried to study the role of this enzyme defect in patients with hematologic malignancies, a population characterized by deep grade immunosuppression. Bacterial infections are the leading cause of morbidity and mortality in hematologic patients with neutropenia. Fluoroquinolone prophylaxis was proved to be the only effective strategy to reduce febrile neutropenia, but the safety of this class of agents in patients with G6PD deficiency is questionable because of a claimed association with AHA. I retrospectively analyzed 242 patients treated with 628 intensive chemotherapy courses; 59 patients presented G6PD deficiency. All patients underwent fluoroquinolone prophylaxis. The primary endpoint was incidence of AHA. Secondary endpoints were incidence of febrile neutropenia, microbiologically and clinically documented infections and incidence of Gram Positive or Gram Negative infections. No episode of AHA was observed in the entire cohort. Incidence of microbiologically and clinically documented infection was similar, but incidence of invasive fungal disease (IFD; p