Radiation Biodosimetry in Patients Treated With Total Body Irradiation (TBI)
- To validate and refine three methods of rapid high throughput radiation biodosimetry
using peripheral blood and urine from patients undergoing total-body irradiation
preceding hematopoietic stem cell transplantation, including miniaturization and
automation of cytogenetic and immunofluorescence assays, development and testing of
gene expression profiles for use as biodosimeters and their incorporation into a
self-contained test cassette, and profiling urinary metabolites that are specific for
radiation exposure and dose.
- To gain mechanistic insight into potentially different responses to radiation between
mice and humans, and between ex vivo and in vivo irradiation.
OUTLINE: This is a multicenter study.
Patients undergo blood and optional urine sample collection before the start of the first
total-body irradiation (TBI) treatment, 4-8 hours after the first TBI (but before the
second), and 24 hours after the first TBI treatment. Samples are analyzed for RNA extraction
and subsequent microarray analysis. Some patients may have additional blood samples
collected prior to TBI for validation studies, at the discretion of the investigator.
Samples are analyzed for micronucleus formation and γH2AX focus formation to assess whether
blood irradiation in vivo demonstrates a different biological response to blood irradiated
ex vivo. An additional blood sample is obtained at the first time point (prior to TBI
irradiation) and stored for future correlative studies. Samples are analyzed using
cytogenetic, protein, metabolic, and gene expression assays.
Patient medical records are obtained and reviewed for age, gender, race, ethnicity,
diagnosis, disease status, cytogenetics, HLA typing data, prior treatment (chemotherapy and
radiotherapy), pre-transplant disease-specific data such as blood counts, metabolic
profiles, co-existing disease at the time of transplant, history of infection exposure prior
to transplant, former and active medical problems (with prior and active therapies, both
prescribed and over-the-counter, including herbals, vitamins and dietary supplements),
functional status, organ function prior to transplant, special or unusual dietary history,
history of tobacco, alcohol or illicit drug use, carcinogen/toxin/teratogen/mutagen exposure
history, and infectious disease markers for hepatitis B and C, syphilis, HIV, CMV, HTLV
Validation and refinement of three methods of rapid high throughput radiation biodosimetry
Suzanne Wolden, MD
Memorial Sloan-Kettering Cancer Center
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|