Study on Fractionated Total Body Irradiation before Hematopoietic Stem Cell Transplantation

Discussion

TBI is an important part of pretreatment for hematopoietic stem cell transplantation. Its main effects include the followings: i) immunosuppression used in order that the new cells can be accepted by the donee^[2]; ii) removing the malignant tumor cells, which have escaped from chemotherapy^[3]; iii) killing bone marrow cells so that transplant may be accepted; iv) to destroy tumor cell multidrug resistance of the primary tumor, and v) significantly increase to the radiation sensitive of leukemia and lymphoma cells of destruction.

TBI is a special radiotherapy technology that produces many questions related to clinical medicine, radiation biology, physics etc. Although it has been in practice more than 50 years, there are still many questions. To increase the survival rate and reduce the recurrence rate as well as the incidence of interstitial pneumonitis (IP), staff from many blood transplant centers have studied the use of the single and fractionated-dose TBI treatments, and then once more the single and fractionated TBI treatment models and dose fractions^[4,5]. Now, at the international level, there is no unified standard for TBI dosage. Experimental studies and clinical data have confirmed that the incidences of IP with single-dose TBI (STBI) is higher than with fractionated (FTBI)^[6,7]. The purpose of FTBI is to decrease normal tissue damage and complications, especially to reduce the incidence of IP. The FTBI may allow an increase in the total dose and improve the therapeutic ratio.

Clinical research has confirmed the cataract incidence of 80% in long-term survivors of STBI to 10 Gy and obviously incidence of FTBI about 10%~20%. FTBI treatment time was short and the patients keeping the body position was easy. The general model of FTBI were 2 Gy/f, 2 f/d, interval 6 to 8 h, TBI total dose was 12 to 14 Gy and 3 Gy/f, 4 f/d or 1.2 Gy/f, 3 f/d, interval 5 h, total dose was 13.2 Gy and 4 Gy/f or 2.5 Gy/f, total dose was 12 Gy^[8]. Our fractional model is total dose is 7~12 Gy, once per day in 2 days. The result indicated that the patients have excellent survivability and gastrointestinal reaction is mildness and hematopoietic reconstitution recovered quickly. The incidence of IP was decreased and graft survival rate was above 70%.

So we think that the FTBI have an advantage contrast with the STBI. The dose of FTBI could be added to 10~12 Gy. Radiobiology research indicated that FTBI could produce a different effect between tumor cells and normal tissue. It conduced to repair the normal tissue and make the treatment effect better than STBI. The model (1 f/d × 2 d) was reasonably. Using the multiple fraction models could not improve incidence of IP, and that increase infection. Besides, it may increase many difficult in the schedule of the radiotherapy department. Devergie et al.^[9] introduced that with the FTBI, the recurrence rate is higher contrast with the STBI about leukemia.

Instantly response of TBI is a serious toxicity including nausea, emeses and dizziness since TBI beginning. Some studies^[10-13] reported that the instantly response occurrence after irradiation 2 to 4 h. The response became seriously accompany irradiation dose increase. Treatment time of STBI was longer and proceeding serious gastrointestinal reaction.

In our study the high dose group was significantly contrast with the low dose group (P < 0.05) of the rate of acute gastrointestinal reaction and oral mucositis. The other reactions were insignificant difference. Several patients were received some antiemetics and sedatives in the first half hour of TBI and the treatment was successfully.

Now people generally recognize this relation between the IP and the total dose and the absorbed dose rate of TBI^[13,14]. With low dose rate irradiation, the treatment would spend more time that the patient is hard to keep position. On the other hand, the TBI may be intermitted because of the acute reaction of nausea and vomiting, etc. Although the high dose rate irradiation would spend less time, the incidence rate of complications were obviously increased, for instance IP.

It is not a linear correlation that between the lungs injury and the reception dose, and exist a critical value between them. Keane^[15] proved a fact that the threshold dose of IP is 7.5 Gy when absorbed dose rate is 0.5~4 Gy/min and the incidence rate of IP add up to 50% when 9.3 Gy. In the low dose rate (1~5 cGY/min) instance, the threshold of IP could be increased to 9 Gy. When Barrett^[16] using the ultra-low dose rate (2.5 cGy/min), the threshold dose could be increased to 9.5 cGy and the IP won’t occurred. In our research the incidence rate for the two groups have not the distinct difference with the same dose rate. It explains that the dose rate is important factor of IP. It is safe and effective when the value of absorbed dose rate is 5 cGy/min and the total dose is 7 Gy~12 Gy. This time the incidence rate of IP is 10%. The difference about the hematopoiesis rebuild and the graft achievement rate between the high dose group and low dose group are insignificantly, and the graft achievement rate is 70%, it is satisfying.