Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation.
OBJECTIVE
Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimens were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity.


METHODS
A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained.


RESULTS
RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease- free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values.


CONCLUSIONS
"More dose is better", provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses.
Kal
Henk B
HB
Department of Radiotherapy Qoo118, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. H.B.Kal@UMCUtrecht.nl
Loes van Kempen-Harteveld
M
M
Heijenbrok-Kal
Majanka H
MH
Struikmans
Henk
H
D016001:Confidence Intervals; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007668:Kidney / Q000528:radiation effects*; D007908:Lens, Crystalline / Q000528:radiation effects*; D007938:Leukemia / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D008168:Lung / Q000528:radiation effects*; D009364:Neoplasm Recurrence, Local; D011835:Radiation Protection; D016032:Randomized Controlled Trials as Topic; D012062:Relative Biological Effectiveness; D012306:Risk; D013997:Time Factors; D019172:Transplantation Conditioning; D014916:Whole-Body Irradiation