# FRACTIONATED TOTAL BODY IRRADIATION FOR MARROW ABLATION

> **NIH NIH R01** · ALLEGHENY-SINGER RESEARCH INSTITUTE · 1987 · $83,507

## Abstract

Recently, in an effort to reduce leukemia recurrence following marrow
transplantation, several clinical groups have begun applying
fractionated-total-body-irradiation (FTBI) in their preparatory marrow
ablation protocols.  However, the effectiveness of this approach is a
matter of controversy.  The clinical data are conflicting, and the data
from radiobiological models suggest that certain of the approaches to
fractionation may in fact be less effective than the previously used
single-dose TBI.  The original (and most effective) single-dose TBI marrow
ablation protocols were patterned after mouse models in which their ability
could be directly tested by CFU-S assays.  However, most of the current
FTBI protocols have been derived empirically in the clinic without testing
in a model, and there is reason to believe from radiobiological
considerations that some of these may not be sound in their design.  On the
other hand, it is also the case that when cytotoxic drugs are combined with
TBI the effect on hematopoietic stem cell survival may not be predictable
on the basis of radiation considerations alone.  It is therefore possible
that certain FTBI protocols in which drug-radiation interactions occur may
offer a therapeutic gain in marrow ablation over single-dose TBI
protocols.  Which types of combinations might offer such a gain also are
not wholely predictable on the basis of empirical considerations.  However,
their potential effectiveness as a class can be straight-forwardly
evaluated in a mouse model where stem cell survival can be directly
measured by CFU-S techniques.  Using such a model, involving normal mice
and three different murine leukemia strains, we propose to evaluate by
means of CFU-S assays--which will be followed by transplantation
studies--the effectiveness of FTBI applied in three fashions:  Before
drugs; After drugs; and Interspersed with drugs.  The data obtained with
the leukemic models will be compared against their normal controls both in
terms of CFU-S response, and in terms of overall differences in
hematopoietic cell kinetics between the normal and leukemic tissues which
could affect their manner of response.  The results obtained with the FTBI
will be compared to similar regimens where the total of the TBI is applied
as a single-dose to determine if, and under what conditions, FTBI plus
drugs may result in a therapeutic gain for marrow ablation over single-dose
TBI plus drugs.

## Key facts

- **NIH application ID:** 3175425
- **Project number:** 5R01CA037643-03
- **Recipient organization:** ALLEGHENY-SINGER RESEARCH INSTITUTE
- **SAM.gov UEI:** F7V2DLFLWJN9
- **Principal Investigator:** JAMES P OKUNEWICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $83,507
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175425

## Citation

> US National Institutes of Health, RePORTER application 3175425, FRACTIONATED TOTAL BODY IRRADIATION FOR MARROW ABLATION (5R01CA037643-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175425. Licensed CC0.

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