**4. Radiobiological considerations for Total Body Irradiation**

The techniques and methodology described in the previous section account for the physical criteria and limitations for the TBI procedure. The actual dose prescription and dose delivery schedule also play an important role in the success of the procedure (Shank, 1999). Normal lymphocytes are among the most radiosensitive cells and become profoundly depleted with TBI (Shank, 1999). In addition to finding that TBI was more immunosuppressive than CY, Shank describes early animal studies that found the degree of immunosuppression was a function of the total radiation dose. Dividing the treatment into multiple fractions over several days required an increase in total dose to achieve consistent results. Shank states the need for an increased dose over a fractionated schedule implies repair processes occurring between fractions.

Radiobiologists categorize the repair process from fractionated radiation treatments as repair, reoxygenation, redistribution and repopulation (Evans, 2000). In the context of TBI as applied to bone marrow transplantation, Evans states repair and repopulation are probably the most significant of these processes and can be best explained with a cell survival curve as shown in Figure 6. The slope of a survival curve can describe the radiation sensitivity of a particular cell type. The slope of the curve, termed Do and the shoulder region, termed Dq, quantify significant parameters of a cells response to radiation. Cells from different tissues have different Do's and Dq's as illustrated in Figure 6.

It has been generally accepted that a small shoulder (Dq) is typical of bone marrow stem cells and leukemia cells (Evans, 2002). Therefore, these cells have a limited ability to repair damage. In contrast, cells of lung tissue and intestinal epithelial cells have survival curves with must broader shoulders (Dq), implying a greater repair capacity. The second important repair process is repopulation. Evans defines repopulation as the proliferation of cells between dose fractions. Rapidly dividing tissues, like the intestine, can increase their normal proliferation rate after a radiation treatment. Slowly dividing tissues such as the lung and vascular tissues tend not to proliferate at a higher rate after radiation. Therefore, during a fractionated radiation therapy regimen, Evans speculates that both repair and repopulation may occur between fractions. Repair of the leukemia cells is minimal. The separation of the leukemia cell survival curve from the lung cell survival curve increases the therapeutic ratio and supports fractionation. Shank (1998) attempted to calculate the optimal TBI schedule including fraction dose, number of fractions, and total dose. In addition, Shank reviews some clinical trials with regards to percentage relapse with different TBI schedules. Shank summarizes her findings that the greatest leukemia cell kill with minimum morbidity will occur with a highly fractionated radiotherapy regimen. A total dose of 1400-1500 cGy delivered over 10-13 fractions may be optimal.

Despite efforts to provide a comfortable treatment in the TBI stand, the opposed lateral TBI table still is viewed as the most comfortable for patients and easy to set up. Patients receiving TBI that requires dose reduction to the lungs and/or liver are treated using a combination of these two techniques. All current protocols requiring dose reduction to these organs require treatments to be administered over four days or 8 fractions. We routinely treat 4 fractions with the AP/PA TBI stand technique and 4 fractions with the opposed

The techniques and methodology described in the previous section account for the physical criteria and limitations for the TBI procedure. The actual dose prescription and dose delivery schedule also play an important role in the success of the procedure (Shank, 1999). Normal lymphocytes are among the most radiosensitive cells and become profoundly depleted with TBI (Shank, 1999). In addition to finding that TBI was more immunosuppressive than CY, Shank describes early animal studies that found the degree of immunosuppression was a function of the total radiation dose. Dividing the treatment into multiple fractions over several days required an increase in total dose to achieve consistent results. Shank states the need for an increased dose over a fractionated schedule implies

Radiobiologists categorize the repair process from fractionated radiation treatments as repair, reoxygenation, redistribution and repopulation (Evans, 2000). In the context of TBI as applied to bone marrow transplantation, Evans states repair and repopulation are probably the most significant of these processes and can be best explained with a cell survival curve as shown in Figure 6. The slope of a survival curve can describe the radiation sensitivity of a particular cell type. The slope of the curve, termed Do and the shoulder region, termed Dq, quantify significant parameters of a cells response to radiation. Cells from different tissues

It has been generally accepted that a small shoulder (Dq) is typical of bone marrow stem cells and leukemia cells (Evans, 2002). Therefore, these cells have a limited ability to repair damage. In contrast, cells of lung tissue and intestinal epithelial cells have survival curves with must broader shoulders (Dq), implying a greater repair capacity. The second important repair process is repopulation. Evans defines repopulation as the proliferation of cells between dose fractions. Rapidly dividing tissues, like the intestine, can increase their normal proliferation rate after a radiation treatment. Slowly dividing tissues such as the lung and vascular tissues tend not to proliferate at a higher rate after radiation. Therefore, during a fractionated radiation therapy regimen, Evans speculates that both repair and repopulation may occur between fractions. Repair of the leukemia cells is minimal. The separation of the leukemia cell survival curve from the lung cell survival curve increases the therapeutic ratio and supports fractionation. Shank (1998) attempted to calculate the optimal TBI schedule including fraction dose, number of fractions, and total dose. In addition, Shank reviews some clinical trials with regards to percentage relapse with different TBI schedules. Shank summarizes her findings that the greatest leukemia cell kill with minimum morbidity will occur with a highly fractionated radiotherapy regimen. A total dose of 1400-1500 cGy

**4. Radiobiological considerations for Total Body Irradiation** 

**3.4 Combination of treatment methods** 

repair processes occurring between fractions.

have different Do's and Dq's as illustrated in Figure 6.

delivered over 10-13 fractions may be optimal.

lateral TBI table option.

Fig. 6. A typical survival curve for mammalian cells exhibiting an initial shoulder followed by an exponential region. An initial shoulder characterizes the curve with some slope to it (1Do), the exponential slope (Do), n (extrapolation number) and Dq.
