PET/CT and Bacterial/Fungal PCR in High Risk Febrile Neutropenia (PIPPIN)

Early Diagnosis and Treatment of Infections in Patients With Haematologic Malignancies: Examining Novel Diagnostics Including Bacterial and Fungal Multiplex PCR and FDG-PET Imaging

Patients with acute leukaemia requiring induction or consolidation chemotherapy and those requiring a haematopoietic stem cell transplant are at high risk of fever and infection when they have low white cell counts (neutropenic fever). The causes of neutropenic fever are frequently unknown and patients are treated with broad antibiotics, without a clear target to what is being treated. This study will prospectively enroll patients who are receiving chemotherapy for acute leukaemia or for a stem cell transplant and compare the diagnostic utility of bacterial and fungal PCR performed directly off blood drawn, to the standard blood culture. Patients who have persistent fever after 72 hours of antibiotics will then be randomized to have either the interventional scan (PET/CT) or the conventional scan (standard CT) to look for a source of infection. Diagnostic yield, change in management and outcomes will be compared between arms.

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Haematopoietic Stem Cell Transplant, Autologous, Haematopoietic Stem Cell Transplant, Allogeneic, Febrile Neutropenia

Participants with persistent febrile neutropenia after 72 hours of onset who are randomized to this arm will have an FDG-PET/CT performed to look for source of fever.

Participants with persistent febrile neutropenia after 72 hours of onset who are randomized to this arm will have a conventional CT (HRCT chest and sinuses +/- other regions as per clinician's discretion) performed to look for source of fever.

Defined as: referral for targeted sampling, referral for surgery change in antimicrobial therapy removal of a central line

The duration (in days) of hospital length of stay for the episode in which neutropenic fever occurred

The proportion of patients in each arm who were admitted to intensive care during their admission in which neutropenic fever occurred

The proportion of patients per arm who have passed away during the admission in which neutropenic fever occurred

Inclusion Criteria: About to have an allogeneic haematopoietic stem cell transplant, OR About to have an autologous haematopoietic stem cell transplant, OR Commencing induction or consolidation chemotherapy with curative intent for acute myeloid or acute lymphoid leukaemia Exclusion Criteria: Current actively diagnosed infection prior to transplant or chemotherapy Allergy to intravenous contrast for CT imaging eGFR <30 Pregnant

Douglas A, Thursky K, Spelman T, Szer J, Bajel A, Harrison S, Tio SY, Bupha-Intr O, Tew M, Worth L, Teh B, Chee L, Ng A, Carney D, Khot A, Haeusler G, Yong M, Trubiano J, Chen S, Hicks R, Ritchie D, Slavin M. [18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Haematol. 2022 Aug;9(8):e573-e584. doi: 10.1016/S2352-3026(22)00166-1. Epub 2022 Jun 28.